Sample records for 99m clearance curves

Major sources of errors in the gamma-camera methods for the calculation of renal clearance are the accuracy of background correction for obtaining the true renal time-activity curve and the validity of the externally recorded pre-cordial activity as an estimate of the plasmatic time-activity curve. With technetium 99m mercaptoacetyltriglycine (99mTc-MAG3), because of its high protein plasma binding, one could expect minimal extravascular diffusion and hence a more accurate externally detected plasmatic curve. The high extraction rate should reduce the influence of the background, but, on the other hand, the effect of hepatobiliary excretion on the calculation of renal clearance might be significant. Our results suggest that the hepatobiliary excretion of 99mTc-MAG3 does not influence the gamma-camera renal clearance determination, even in patients with low renal function. However, the pre-cordial curve does not reflect accurately the plasmatic disappearance curve; its calibration with a single plasma sample taken at the 20th min is responsible for significant errors, probably because of an unfavourable ratio between the intravascular and extravascular activities at the 20th min. (orig.)

Experiments were performed to determine the effects of conventional mechanical ventilation (CMV) and high-frequency oscillation (HFO) on the clearance of technetium-99m-labeled diethylenetriamine pentaacetate (/sup 99m/Tc-DTPA) from lungs with altered surface tension properties. A submicronic aerosol of /sup 99m/Tc-DTPA was insufflated into the lungs of anesthetized, tracheotomized rabbits before and 1 h after the administration of the aerosolized detergent dioctyl sodium sulfosuccinate (OT). Rabbits were ventilated by one of four methods: 1) spontaneous breathing; 2) CMV at 12 cmH2O mean airway pressure (MAP); 3) HFO at 12 cmH2O MAP; 4) HFO at 16 cmH2O MAP. Administration of OT resulted in decreased arterial PO2 (PaO2), increased lung wet-to-dry weight ratios, and abnormal lung pressure-volume relationships, compatible with increased surface tension. /sup 99m/Tc-DTPA clearance was accelerated after OT in all groups. The post-OT rate of clearance (k) was significantly faster (P less than 0.05) in the CMV at 12 cmH2O MAP [k = 7.57 +/- 0.71%/min (SE)] and HFO at 16 cmH2O MAP (k = 6.92 +/- 0.61%/min) groups than in the spontaneously breathing (k = 4.32 +/- 0.55%/min) and HFO at 12 cmH2O MAP (4.68 +/- 0.63%/min) groups. The clearancecurves were biexponential in the former two groups. We conclude that pulmonary clearance of /sup 99m/Tc-DTPA is accelerated in high surface tension pulmonary edema, and this effect is enhanced by both conventional ventilation and HFO at high mean airway pressure

Pneumocystis carinii pneumonia (PCP) has become a major cause of morbidity and mortality due to infectious diseases, largely as a result of the acquired immunodeficiency syndrome (AIDS) epidemic. Since the mortality from recurrent infection is between 40% and 60%, early diagnosis and therapy are the keys to survival. The role of technetium 99m diethylenetriaminepentacetate (DTPA) aerosol pulmonary clearance was studied in 81 patients with AIDS. The mathematical technique of curve stripping was found to be the optimal method of analysis and to provide an overall sensitivity of 94% for the detection of interstitial pneumonitis. The procedure was superior to standard pathology parameters and radiography and more convenient than gallium 67 scintigraphy. (orig.)

Alterations in regional epithelial permeability were assessed in 22 retired West Virginia coal miners' lungs by measuring the clearance of inhaled 0.5-μm Tc-99m DTPA aerosol. Activity was measured in both lungs and in regions of interest placed over the lung periphery in the apical, middle, and basal portions of each lung. Clearance rates (T/sub 1/2/) for 5 nonsmokers, 8 ex-smokers, and 9 smokers were significantly faster than for comparable subjects measured elsewhere, who were not coal miners. Regional apex-to-base distributions of DTPA were measured as a function of clearance time and compared with regional ventilation and perfusion. Regional, as well as overall lung clearancecurves of 8 smokers and 4 ex-smokers had two components, with overall T/sub 1/2/ of 2. The results of our study suggest that measurement of DTPA clearance is a potentially useful noninvasive technique to assess lung injury in miners exposed to coal dust. 14 refs., 6 figs., 2 tabs

Alveolar epithelial permeability was assessed in 32 patients with progressive systemic scleroderma (PSS), using 99mTc-DTPA aerosol. Immediately after the inhalation of 99mTc-DTPA aerosol for 3 to 6 minutes under normal tidal breathing, lung was imaged sequentially for 30 minutes from the posterior by a gamma camera and exponential fitting was processed on the time activity curve. T1/2 (min) was used as a parameter for the evaluation of permeability of alveolar epithelium. Patients with collagen disease showed shorter T1/2 (T1/2=43.7±23.8 min) than the normal volunteers (T1/2=76.8±8.7 min). No significant difference was observed between patients with or without interstitial changes on the chest CT. Significant correlation was not observed between T1/2 and %VC or %DLco. In 8 cases, studies were repeated in the interval of 3 to 19 months. Improvement of T1/2 was seen in 4 cases, independent of CT findings. These results suggest that 99mTc-DTPA aerosol clearance study provides information independent from other lung examinations, and may be useful for the assessment of lung interstitial changes in patients with PSS. (author)

The authors measured clearance of 99mTc-labeled diethylenetriamine pentaacetic acid (99mTc-DTPA) in rabbits with experimentally increased alveolar surfactant content. In one group of animals, surfactant production was increased by treatment with ambroxol, and another group of animals was treated with tracheal instillation of natural surfactant. A group of untreated control animals and animals treated with instillation of saline were also studied. Clearance was measured during standard conditions of mechanical ventilation and during ventilation with large tidal volumes. In ambroxol- and surfactant-treated groups, clearance rate was reduced compared with untreated control animals. In contrast, clearance rate increased after saline instillation. The differences were observed at both modes of ventilation. The findings indicate that the pulmonary surfactant system is a rate-limiting factor for the clearance of 99mTc-DTPA and that the volume dependence of clearance is not explained by stretching of the alveolar wall only. 28 refs., 2 figs., 1 tab

Many studies have reported clearance rates of 99mTc-DTPA from the alveolar epithelial surface, but few have measured clearance of this solute from the bronchial mucosa. Those that have attempted such measurements have discounted the possibility that 99mTc-DTPA may be removed from the bronchial airways by mucocilliary transport as well as by absorption through the epithelium. This study was designed to better approximate the rate of 99mTc-DTPA absorption across the bronchial epithelium by correcting the measurements of total 99mTc-DTPA clearance for mucus transport. On two separate study days, each normal, nonsmoking subject (n = 8) breathed an aqueous aerosol (2.0 microns MMAD, sigma g = 2.0) containing 99mTc bound to DTPA or human serum ablumin (HSA) (a relatively nonpermeable solute that is cleared only by mucus transport over the period of measured clearance) while seated in front of a gamma camera. Breathing pattern was standardized to produce a similar central deposition of particles on both study days. From measurements of retention versus time over a 1-h period, exponential rate constants (Ktot and Km) were determined for the clearance of 99mTc-DTPA and 99mTc-HSA, respectively. By modeling the airways as a single compartment with two possible routes of clearance, we determined the permeability rate constant, Kp, as Ktot minus Km. Results showed that mucus clearance (Km) accounted for two thirds of the total rate of 99mTc-DTPA clearance (Ktot) (mean Ktot = 0.00985, Km = 0.00698, and Kp = 0.00287/min)

There are a few reports about usefulness of {sup 99m}Tc-GSA liver scintigraphy (GSA imaging) for the evaluation of postoperative state of biliary atresia. However, comparison of significance for the disease between GSA imaging and {sup 99m}Tc-PMT hepatobiliary imaging have not been reported. Fifty-six GSA imagings for 41 postoperative biliary atresia patients were reviewed and their scintigraphic findings and the functional parameters were compared with those obtained from {sup 99m}Tc-PMT hepatobiliary imaging. In quantitative analysis, although the hepatic clearance of both tracers calculated by graphical analysis (Patlak plot) were well correlated in most cases, a discrepancy was observed in several cases with jaundice. The authors conclude that the hepatic clearance of {sup 99m}Tc-GSA is a more accurate index of the hepatic reserve than that of {sup 99m}Tc-PMT which can be influenced by hyperbilirubinemia and that the combination of both examinations is helpful to evaluate development of liver injury in postoperative biliary atresia patients. (author)

There are a few reports about usefulness of 99mTc-GSA liver scintigraphy (GSA imaging) for the evaluation of postoperative state of biliary atresia. However, comparison of significance for the disease between GSA imaging and 99mTc-PMT hepatobiliary imaging have not been reported. Fifty-six GSA imagings for 41 postoperative biliary atresia patients were reviewed and their scintigraphic findings and the functional parameters were compared with those obtained from 99mTc-PMT hepatobiliary imaging. In quantitative analysis, although the hepatic clearance of both tracers calculated by graphical analysis (Patlak plot) were well correlated in most cases, a discrepancy was observed in several cases with jaundice. The authors conclude that the hepatic clearance of 99mTc-GSA is a more accurate index of the hepatic reserve than that of 99mTc-PMT which can be influenced by hyperbilirubinemia and that the combination of both examinations is helpful to evaluate development of liver injury in postoperative biliary atresia patients. PMID:9916401

The effect of α-naphthylisothiocyanate (ANIT) on blood clearance of 99mTc-phytate (99mTc-P) in dogs was examined, and blood clearance test of 99mTc-P was compared with the cases of serum transaminase test or serum bilirubin test. Serum transaminase and bilirubin levels in dogs increased after ANIT administration, however, the degree of increase in these parameters was much lower than the cases in rats. The disappearance rate of 99mTc-P from blood in dogs decreased with the increase in dose of ANIT and with the passage of time after the ANIT administration. Changes of the blood clearance of 99mTc-P after ANIT treatment in dogs may be influenced by the disorder in the hepatocytes rather than in the bile ductule cells. The blood clearance test of 99mTc-P in dogs showed a sensitive reaction for the acute hepatic dysfunction induced by ANIT equally to the serum transaminase test or the serum bilirubin test. (author)

The effect of D-galactosamine (GalN) on the blood clearance of 99mTc-phytate (99mTc-P) in dogs was examined, and the blood clearance test of 99mTc-P was compared with the cases of the serum transaminase and bilirubin test. Serum transaminase and bilirubin levels in dogs increased dose-dependently after GalN administration, and the degree of increase in these parameters was much higher than the cases in rats. The disapearance rate of 99mTc-P from blood in dogs decreased with the increase in dose of GalN and with the passage of time after the GalN administration. Changes of the blood clearance of 99mTc-P after GalN treatment in dogs may be influenced by the disorder in the hepatocytes. The blood clearance test of 99mTc-P in dogs showed a sensitive reaction for the acute hepatic dysfunction induced by GalN equally to the serum transaminase and bilirubin test. (author)

The permeability of the alveolar-capillary barrier to an inhaled aerosol of technetium 99m labelled diethylenetriamine penta-acetate (99mTc-DTPA is used as an index of alveolar epithelial injury. Permeability is greatly increased in active smokers. The aim of this study was to determine the effect of sidestream smoke inhalation on permeability as this has not been described previously. Lung clearance of inhaled 99mTc-DTPA aerosol was measured in 20 normal non-smoking subjects before and after exposure to one hours sidestream smoke inhalation. Measured carbon monoxide (CO) levels rose to a maximum of 23.5 ±6.2 ppm from baseline values of 0.6±1.3 (p99mTc-DTPA clearance rose from baseline 69.1± 15.6 (mean ± to 77.4 ±17.8) after smoke exposure. No effect of 99mTc-DTPA scanning of sidestream smoke was demonstrated on lung function. It was concluded that low level sidestream smoke inhalation decreases 99mTc-DTPA clearance acutely in humans. The mechanism of this unexpected result is not established but may include differences in constituents between sidestream and mainstream smoke, alterations in pulmonary microvascular blood flow, or changes in surfactant due to an acute phase irritant response. 34 refs., 2 figs

We investigated the dose-response effect of positive end-expiratory pressure (PEEP) and increased lung volume on the pulmonary clearance rate of aerosolized technetium-99m-labeled diethylenetriaminepentaacetic acid (99mTc-DTPA). Clearance of lung radioactivity was expressed as percent decrease per minute. Base-line clearance was measured while anesthetized sheep (n = 20) were ventilated with 0 cmH2O end-expiratory pressure. Clearance was remeasured during ventilation at 2.5, 5, 10, 15, or 20 cmH2O PEEP. Further studies showed stepwise increases in functional residual capacity (FRC) (P less than 0.05) measured at 0, 2.5, 5, 10, 15, and 20 cmH2O PEEP. At 2.5 cmH2O PEEP, the clearance rate was not different from that at base line (P less than 0.05), although FRC was increased from base line. Clearance rate increased progressively with increasing PEEP at 5, 10, and 15 cmH2O (P less than 0.05). Between 15 and 20 cmH2O PEEP, clearance rate was again unchanged, despite an increase in FRC. The pulmonary clearance of aerosolized /sup 99m/Tc-DTPA shows a sigmoidal response to increasing FRC and PEEP, having both threshold and maximal effects. This relationship is most consistent with the hypothesis that alveolar epithelial permeability is increased by lung inflation

Plasma clearance and plasma protein bonding of two different 99mTc pyrophosphate preparates with different content of pyrophosphate, as well as of a 99mTc diphosphonate preparate were investigated in patients who have undergone a routine scintiscanning of the skeleton. Strontium 85 was used as comparative standard for all patients. The plasma protein compound was determined by salting out the plasma proteins with a saturated ammonium sulphate solution and with a molecular filter. The overall blood activity was also determined for part of the patients. The lowest plasma protein bonding and the fastest plasma clearance was found in the diphosphonate preparate, the highest plasma protein bonding and slowest plasma clearance in the pyrophosphate preparate with the lowest pyrophosphate content. The slowest plasma clearance altogether was found in 85Sr for which the plasma protein bonding could not be measured. The conclusion in drawn that the different plasma clearance of the different 99m technetium phosphate complexes is caused by a varying protein bonding. The protein bonding is explained by the instability of the bone-seeking 99mTc phosphate complexes which at low concentrations in the plasma is converted into a non-bone-seeling 99mTc compound with high protein bonding. The different behaviour of the diphosphonate and pyrophosphate complex is traced back to a varying stability in the plasma. By adding larger amounts of pyrophosphate, the stability of 99mTc pyrophosphate in the plasma can be improved upon, this results in an improved plasma clearance and lower plasma protein bonding. (orig./MG)

The 99mTc-DTPA aerosol inhalation method permits detection of pulmonary epithelial damage. We investigated one of several problems, airway deposition of inhaled aerosol, on the assessment of pulmonary epithelial permeability in healthy nonsmokers and patients with interstitial lung diseases. We used the rate constant of pulmonary 99mTc-DTPA clearancecurve, k, as a parameter of the epithelial permeability. The alveolar-peripheral airway deposition of aerosol was estimated by the duplicated inhalation method, which we newly developed. The mean k in patients with interstitial lung disease (2.52±0.72%/min, n=8; pc) was higher in patients with interstitial lung disease (4.08±1.63%/min; pc in both groups (pc obtained among the subjects (r=0.951; p99mTc-DTPA aerosol inhalation method although the correction was significant in the individual subjects. (author)

We measured the pulmonary clearance of inhaled 99mTc-DTPA and 99mTc-albumin in rabbits with surfacant dysfunction induced by dioctyl sodium sulphosuccinate and in rabbits with lung injury induced by oleic acid. After inhalation of 99mTc-albumin in ten animals, clearance of the tracer from the lungs was monitored for 90 min. The first 30 min was a control period. Dioctyl sodium sulphosuccinate was then administered in aerosol and after another 30 min oleic acid was injected intravenously. Ten other rabbits were given 99mTc-DTPA, and clearance was externally recorded for 60 min. Five animals inhaled detergent aerosol and five animals were given oleic acid intravenously after 30 min. Airway pressures, tidal volume, and arterial blood gases were measured before and after each intervention. The half-life of 99mTc-albumin in the lung was 442 ± 123 min during the control period, 363 ± 52 min after detergent administration, and 134 ± 18 min after oleic acid administration. The half-life of 99mTc-DTPA was 94 ± 16 min before and 10 ± 0.6 min after detergent administration and 75 ± 12 min before and 18 ± 1.8 min after oleic acid administration. Gas exchange was not affected by administration of dioctyl sodium sulphosuccinate but markedly impaired after injection of oleic acid. Compliance of the respiratory system remained unaffected by detergent but decreased after injection of oleic acid. The results indicate that the rate limiting factors for the alveolo-capillary transfer of 99mTc-albumin and 99mTc-DTPA are different. Surfactant dysfunction affects the transfer of 99mTc-DTPA but not 99mTc-albumin. (author)

The effects of intensive prolonged exercise on the pulmonary clearance rate of aerosolized 99mTc-labeled diethylenetriaminepentaacetate (99mTc-DTPA) and pulmonary mechanics were studied in seven healthy nonsmoking volunteers. 99mTc-DTPA clearance and pulmonary mechanics (lung volumes and compliance) were assessed before and after 75 min of constant-load exercise performed on a treadmill, corresponding to 75% of maximal O2 uptake. Because both clearance measurements were made in similar conditions of pulmonary blood flow, respiratory rate, and tidal volume, changes in clearance rate can be assumed to represent changes of alveolar epithelial permeability. After exercise, total, apical, and basal clearance were significantly increased (P less than 0.01, 0.05, and 0.05, respectively) and the increases in total clearance and tidal volume observed during exercise were significantly correlated (P less than 0.05). In contrast, no significant change was found in pulmonary mechanics. These results show that prolonged intensive exercise induces an increase in epithelial permeability, which appears to be related to the mechanical effects of sustained increased ventilation. Because no change was evidenced in pulmonary volumes or in lung elasticity, our results suggest that this increase may result from alteration of the intercellular tight junctions rather than from a surfactant deficiency

Although positive airway pressure is often used to treat acute pulmonary edema, the effects on epithelial solute flux are not well known. We measured independently the effect of 1) positive pressure and 2) voluntary hyperinflation on the clearance of inhaled technetium-99m-labeled diethylenetriaminepentaacetic acid (/sup 99m/Tc-DTPA) in six nonsmokers and six smokers. Lung volumes were monitored by inductance plethysmography. Each subject was studied in four situations: 1) low end-expiratory volume (LO-), 2) low volume plus 9 cmH2O continuous positive airway pressure (LO+), 3) high end-expiratory volume (HI-), and 4) high volume plus continuous positive airway pressure (HI+). The clearance half time of 99mTc-DTPA for the nonsmokers decreased from 64.8 +/- 7.0 min (mean +/- SE) at LO- to 23.2 +/- 5.3 min at HI- (P less than 0.05). Positive pressure had no synergistic effect. The mean clearance half time for the smokers was faster than nonsmokers at base line but unaffected by similar changes in thoracic volume and pressure. We conclude that, in nonsmokers, positive airway pressure increases /sup 99m/Tc-DTPA clearance primarily through an increase in lung volume and that smokers are immune to these effects.

The lung clearance of Tc 99m DTPA is generally attributed to the degree of distension of the interepithelial junctions and thus of the alveoli. To assess this hypothesis a submicronic aerosol of Tc 99m DTPA (0.5 μ mass median diameter) was inhaled by eight non smoking volunteers placed in left lateral decubitus (LLD) where the alveoli of the left lung are compressed and those of the right lung expanded. The lung radioactivity was followed with a gamma camera 15 minutes in LLD, then 15 minutes in right lateral decubitus (RLD) to reverse the relative distension of the alveoli. Regional clearances were computed on each lung divided in three horizontal slices. These results suggest that alveolar distension has a major role in the DTPA clearance which is relatively independent of the initial deposition of the aerosol

Full Text Available The early demonstration of lung involvement in systemic lupus erythematosus (SLE patients is a difficult but important task. In the present study we attempted to identify abnormalities in pulmonary clearance of 99mTc-DTPA in SLE, correlating their clearance data with clinical findings and disease activity. Forty-six consecutive SLE patients with and without active disease (LACC score and 30 normal volunteers were studied. All subjects were submitted to pulmonary scintigraphy with 99mTc-DTPA to evaluate the pulmonary clearance, and to a chest X-ray, and SLE patients were submitted to tests of disease activity, spirometry, arterial blood gases and tests to assess acute-phase proteins. Pulmonary clearance was faster in SLE patients with active disease when compared to normal controls [half-life of 67.04 min (51.52-82.55 min in active SLE versus 85.87 min (78.85-92.87 min in controls, P<0.05] and there was a higher frequency of abnormal clearance rates in patients with active disease (11 of 26 patients, 42.3% when compared with SLE patients without disease activity (2 of 20 patients, 10% (P = 0.04. A significant correlation was observed between the clearance rates and cough (P<0.05, but not between the clearance rates and dyspnea symptoms or radiological findings, duration of SLE disease, antinuclear antibody titers and patterns, C-reactive protein or anti-double stranded DNA antibodies. We conclude that the pulmonary clearance of 99mTc-DTPA is increased in SLE patients with active disease.

The early demonstration of lung involvement in systemic lupus erythematosus (SLE) patients is a difficult but important task. In the present study we attempted to identify abnormalities in pulmonary clearance of 99mTc-DTPA in SLE, correlating their clearance data with clinical findings and disease activity. Forty-six consecutive SLE patients with and without active disease (LACC score) and 30 normal volunteers were studied. All subjects were submitted to pulmonary scintigraphy with 99mTc-DTPA to evaluate the pulmonary clearance, and to a chest X-ray, and SLE patients were submitted to tests of disease activity, spirometry, arterial blood gases and tests to assess acute-phase proteins. Pulmonary clearance was faster in SLE patients with active disease when compared to normal controls [half-life of 67.04 min (51.52-82.55 min) in active SLE versus 85.87 min (78.85-92.87 min) in controls, P<0.05] and there was a higher frequency of abnormal clearance rates in patients with active disease (11 of 26 patients, 42.3%) when compared with SLE patients without disease activity (2 of 20 patients, 10%) (P = 0.04). A significant correlation was observed between the clearance rates and cough (P<0.05), but not between the clearance rates and dyspnoea symptoms or radiological findings, duration of SLE disease, antinuclear antibody titers and patterns, C-reactive protein or anti-double stranded DNA antibodies. We conclude that the pulmonary clearance of 99m Tc-DTPA is increased in SLE patients with active disease. (author)

The early demonstration of lung involvement in systemic lupus erythematosus (SLE) patients is a difficult but important task. In the present study we attempted to identify abnormalities in pulmonary clearance of 99mTc-DTPA in SLE, correlating their clearance data with clinical findings and disease activity. Forty-six consecutive SLE patients with and without active disease (LACC score) and 30 normal volunteers were studied. All subjects were submitted to pulmonary scintigraphy with 99mTc-DTPA to evaluate the pulmonary clearance, and to a chest X-ray, and SLE patients were submitted to tests of disease activity, spirometry, arterial blood gases and tests to assess acute-phase proteins. Pulmonary clearance was faster in SLE patients with active disease when compared to normal controls [half-life of 67.04 min (51.52-82.55 min) in active SLE versus 85.87 min (78.85-92.87 min) in controls, P<0.05] and there was a higher frequency of abnormal clearance rates in patients with active disease (11 of 26 patients, 42.3%) when compared with SLE patients without disease activity (2 of 20 patients, 10%) (P = 0.04). A significant correlation was observed between the clearance rates and cough (P<0.05), but not between the clearance rates and dyspnoea symptoms or radiological findings, duration of SLE disease, antinuclear antibody titers and patterns, C-reactive protein or anti-double stranded DNA antibodies. We conclude that the pulmonary clearance of 99m Tc-DTPA is increased in SLE patients with active disease. (author)

The distribution of submicronic particles during cigarette smoking was demonstrated by means of an insoluble (sup(99m)Tc sulfur colloid) aerosol in eleven habitual smokers with no evidence of impaired lung function. Considerable pains were taken to simulate precisely the conditions of their usual smoking. The distribution of aerosol during smoking was compared with that during normal tidal breathing in the same subjects. All subjects showed a shift towards greater apical and central (tracheo bronchial) deposition during smoking as compared with quiet respiration. These findings may be relevant to the apical predominance of centrilobular emphysema and bronchial carcinoma. In a second study the differential clearance of a submicronic sup(99m)Tc DTPA aerosol was studied in a population of habitual smokers immediately after smoking two cigarettes and in a control population. Differential clearance was studied continuously for a period of 60 minutes at several peripheral sites in both lung fields. In non smokers the clearancecurve was monoexponential over the study period. In smokers the curve was biexponential and clearance overall was more rapid than in non smokers as expected. No difference in clearance was seen between the apices and the bases in smokers to correspond to the predominent apical distribution of cigarette smoke particles in either the erect or the supine position. The biexponential clearancecurve in smokers may be due to diffusion of the aerosol from both alveoli and bronchi reflecting the greater central deposition in smokers even though this may not be evident on visual inspection of the aerosol lung scan. (Author)

Experiments were performed to determine the effect of markedly negative pleural pressure (Ppl) or positive end-expiratory pressure (PEEP) on the pulmonary clearance (k) of technetium-99m-labeled diethylenetriaminepentaacetic acid (/sup 99m/Tc-DTPA). A submicronic aerosol containing /sup 99m/Tc-DTPA was insufflated into the lungs of anesthetized intubated sheep. In six experiments k was 0.44 +/- 0.46% (SD)/min during the initial 30 min and was unchanged during the subsequent 30-min interval [k = 0.21 +/- 12%/min] when there was markedly increased inspiratory resistance. A 3-mm-diam orifice in the inspiratory tubing created the resistance. It resulted on average in a 13-cmH2O decrease in inspiratory Ppl. In eight additional experiments sheep were exposed to 2, 10, and 15 cmH2O PEEP (20 min at each level). During 2 cmH2O PEEP k = 0.47 +/- 0.15%/min, and clearance increased slightly at 10 cmH2O PEEP [0.76 +/- 0.28%/min, P less than 0.01]. When PEEP was increased to 15 cmH2O a marked increase in clearance occurred [k = 1.95 +/- 1.08%/min, P less than 0.001]. The experiments demonstrate that markedly negative inspiratory pressures do not accelerate the clearance of /sup 99m/Tc-DTPA from normal lungs. The effect of PEEP on k is nonlinear, with large effects being seen only with very large increases in PEEP

It has been suggested that blood flow have little effect on the lung clearance of Tc-99m DTPA which depends on the alveolar distension. However an increase of pulmonary blood flow, induces a recruitment of new vascular areas which can enhance this clearance. To assess this hypothesis the pulmonary apical and basal clearances of a sumicronic aerosol of Tc-99m DTPA were studied at rest and at exercise in seven non smoking volunteers in upright posture. As a matter of fact exercising upright is known to increase primarily the apical blood flow. After inhalation the subjects were seated on a bicycle their back against a gamma camera which was linked to a computer. The lung radioactivity was registered successively during a resting and an exercising period. At rest there was a gradient of clearance from the apex to the base of the lung, the apical clearance being significantly higher. At exercise (50 Watts, 60 c. min /sup -1/, 7 min.) this regional gradient was enhanced by a large and significant increase of the apical clearances (0.0340 min /sup -1/ +-0.0063 SD versus 0.00183 min /sup -1/ +- 0.074 SD at rest, n = 7, p < 0.01). By contrast the changes of the basal clearances were slight and unsignificant (0.0146 min /sup -1/ +- 0.0062 SD versus 0.0140 min /sup -1/ +- 0.0082 SD). Since exercise induces little distension of the apical alveoli but drastically enhances the apical blood flow, the observed increase of the apical lung clearance could be primarily attributed to the recruitment of new capillaries induced by exercise in the apices. This led to an increase of the surface area permeability product

Abstract Parasite clearance rates are important measures of anti-malarial drug efficacy. They are particularly important in the assessment of artemisinin resistance. The slope of the log-linear segment in the middle of the parasite clearancecurve has the least inter-individual variance and is the focus of therapeutic assessment. The factors affecting parasite clearance are reviewed. Methods of presentation and the approaches to analysis are discussed.

We studied 10 healthy nonsmokers and 8 healthy smokers, in both the upright and supine position, to investigate whether regional differences in respiratory clearance of technetium-99m-labeled diethylenetriamine pentaacetic acid /sup 99m/Tc-DTPA (RC-DTPA) existed and to assess the influence of posture and smoking on the regional RC-DTPA. RC-DTPA was assessed by the lung clearance rates (%/min) of aerosolized /sup 99m/Tc-DTPA (0.8 micron MMD; 2.4 GSD), using data corrected for recirculating radioactivity, in the upper (zone 1), middle (zone 2), and lower (zone 3) posterior lung fields. In nonsmokers, RC-DTPA in zone 1 was faster than in zone 2 or 3 in both the upright (P less than 0.001) and supine positions (P less than 0.0). No effect was produced by changes in posture on the regional RC-DTPA. In smokers, RC-DTPA was increased in all zones compared with the nonsmokers (P = 0.004), with a further increase in RC-DTP in zone 1 in the upright posture compared with the other regions (P less than 0.001). We conclude that in nonsmokers regional RC-DTPA is faster in zone 1 than in other zones, and this is not related to recirculation of radioactivity; posture does not modify the regional RC-DTPA of nonsmokers; smoking increases RC-DTPA in all zones and more in zone 1 in the upright posture

The regional lung clearance of a deposited aerosol of [/sup 99m/Tc] diethylenetriaminepentaacetic acid was successively computed at rest and at exercise in seven nonsmoking volunteers in upright posture. The subjects were seated on a bicycle with their backs against a gamma camera. At rest there was a gradient of clearance from the apex to the base of the lung, the apical clearance being significantly higher. At exercise this regional gradient was enhanced by a large and significant increase of the apical clearances (3.40 +/- 0.63% min-1 s.d. compared with 1.82 +/- 0.75% min-1 s.d. at rest, n = 7, p less than 0.01). By contrast the changes of the basal clearances were slight and unsignificant (1.46 +/- 0.71% min-1 s.d. compared with 1.40 +/- 0.82% min-1 s.d.). This increase of the apical lung clearance could be attributed primarily to the increase of apical blood flow induced by exercise and to the subsequent increase of the permeability surface area product

Six hundred and thirty-nine clearance studies performed in children aged 7 days to 19 years utilizing technetium-99m mercaptoacetyltriglycine (MAG 3) were retrospectively analysed. Standardized conditions for the investigation included: parenteral hydration (60 ml/hxm2 body surface) in addition to normal oral fluid intake, weight-related dose of 99mTc-MAG 3 (1 MBq/kg body weight, minimum 15 MBq) and calculation of clearance according to Bubeck et al. Of the 513 children, 169 included in this analysis could be classified as ''normal'' with regard to their renal function. Normal kidney function was judged by the following criteria: normal GFR for age, normal tubular function (absence of proteinuria and glucosuria), normal renal parenchyma (on ultrasonography, MAG 3 scan and intravenous pyelography), absence of significant obstruction and gross reflux (> grade I) no single kidney and no difference in split renal function > 20%. Results showed increasing MAG 3 clearance values for infants during the first months of life, reaching the normal range for older children and adults between 7 and 12 months. (orig.)

Six hundred and thirty-nine clearance studies performed in children aged 7 days to 19 years utilizing technetium-99m mercaptoacetyltriglycine (MAG 3) were retrospectively analysed. Standardized conditions for the investigation included: parenteral hydration (60 ml/hxm{sup 2} body surface) in addition to normal oral fluid intake, weight-related dose of {sup 99m}Tc-MAG 3 (1 MBq/kg body weight, minimum 15 MBq) and calculation of clearance according to Bubeck et al. Of the 513 children, 169 included in this analysis could be classified as ``normal`` with regard to their renal function. Normal kidney function was judged by the following criteria: normal GFR for age, normal tubular function (absence of proteinuria and glucosuria), normal renal parenchyma (on ultrasonography, MAG 3 scan and intravenous pyelography), absence of significant obstruction and gross reflux (> grade I) no single kidney and no difference in split renal function > 20%. Results showed increasing MAG 3 clearance values for infants during the first months of life, reaching the normal range for older children and adults between 7 and 12 months. (orig.)

Acute cigarette smoke exposure is known to reversibly increase the clearance rate of aerosolized DTPA from human lungs. The authors studied DTPA clearance after acute severe plywood smoke exposure, on the order of that experienced by burn victims, since current diagnostic methods (Xe-133 and radiographs) for major inhalation injury are insensitive and/or non-specific. Smoke generated from burning plywood sawdust and kerosene was delivered via endotracheal tube at 370C. Skin burns were not inflicted (so the pulmonary consequences of thermal injury were not factors). Chest radiographs and Xe-133 studies were obtained before and after smoke injury but before DTPA aerosol delivery. Six normal and 7 smoke-exposed anesthetized mongrel dogs were studied with 3 mCi of Tc-99m DTPA delivered by aerosol for 5 minutes. Pulmonary Tc-99m DTPA activity was quantitated by computer. Data were acquired over the lungs at 1 frame per 10 secs. for 16 minutes, and the t/sub 1/2/ of DTPA washout from the lungs was calculated. The mean t/sub 1/2/ of 6 normal dogs was 36.52 min. (S.D. 17.73), while the t/sub 1/2/ of 7 smoke-injured dogs was 6.08 min. (S.D. 1.99). The longest t/sub 1/2/ of an injured lung (9.68 min.) was slightly more than half of the shortest t/sub 1/2/ of a normal lung (15.36 min). Thus, acutely smoke-injured dog lungs clear Tc-99m DTPA much faster than normal lungs, consistent with an increase in lung epithelial permeability. This technique may be promising clinically, since early diagnosis of inhalation injury is important for optimal therapy

It has been reported that the renal clearance of 99mTc-mercaptoacetyltriglycine (99mTc-MAG3), a newly developed 99mTc-labeled renal tubular agent, effectively reflects renal plasma flow and serves as a useful parameter of renal function. In this study, we investigated on the method for calculating unilateral renal clearance of 99mTc-MAG3 using renal uptake ratio (RUR) and the conversion formula between RUR and renal clearance. Renography by 99mTc-MAG3 was performed in 38 cases with various renal functions and the renal clearance was estimated by three reported methods of one-point-venous-sampling. The results by Bubeck method were most consistent with the individual clinical data. The difference in the methodology of sample measurement or the type of scintillation camera did not affect the values of RUR. The correlation between renal clearance and RUR was not significantly different among the three groups of data acquisition time for RUR, i.e., 1-2 min., 1.5-2.5 min., and 2-3 min. after tracer injection. In summary, Bubeck method and RUR between 1-3 min. after injection seems to be suitable for the establishment or the conversion formula. Using this formula unilateral renal clearance of 99mTc-MAG3 could be reliably estimated without venous sampling. (author)

Background: measurement of absolute or different renal function using radiotracers plays an important role in the clinical management of various renal diseases. Gamma camera quantitative methods is approximations of renal clearance may potentially be as accurate as plasma clearance methods. However some critical factors such as kidney depth and background counts are still troublesome in the use of this technique. In this study the conjugate-view method along with some background correction technique have been used for the measurement of renal activity in99mTc- MAG3 renography. Transmission data were used for attenuation correction and the source volume was considered for accurate background subtraction. Materials and methods: the study was performed in 35 adult patients referred to our department for conventional renography and ERPF calculation. Depending on patients weight approximately 10-15 mCi 99 Tc-MAG3 was injected in the form of a sharp bolus and 60 frames of 1 second followed by 174 frames of 10 seconds were acquired for each patient. Imaging was performed on a dual-head gamma camera(SOLUS; SunSpark10, ADAC Laboratories, Milpitas, CA) anterior and posterior views were acquired simultaneously. A LEHR collimator was used to correct the scatter for the emission and transmission images. Buijs factor was applied on background counts before background correction (Rutland-Patlak equation). gamma camera clearance was calculated using renal uptake in 1-2, 1.5-2.5, 2-3 min. The same procedure was repeated for both renograms obtained from posterior projection and conjugated views. The plasma clearance was also directly calculated by three blood samples obtained at 40, 80, 120 min after injection. Results: 99 Tc-MAG3 clearance using direct sampling method were used as reference values and compared to the results obtained from the renograms. The maximum correlation was found between conjugate view clearance at 2-3 min (R=0.99, R2=0.98, SE=15). Conventional posterior

A radioaerosol based method for measuring MC was introduced. It included an inhalation protocol that resulted in a predominant deposition of radioaerosol in the central bronchi and two simple procedures of evaluation: 1) a visual semi-quantitative bronchoscintigraphic analysis, and 2) a quantitative analysis of the retention of the radioactivity at different points after the inhalation. The results showed that bronchoscintigraphy was a simple technique that may be used to visualize a stimulation of mucociliary transport in the central airways of individuals that do not suffer from too much mucus hypersecretion. Comparison of the MC between individuals, however, should preferably be performed by the method of quantitative analysis of the radioactivity disappearance. A change of MC was found to be one of the first detectable effects on lung function of tobacco smoking. It could be effectively detected by measurement of radioaerosol clearance both by bronchoscintigraphy and simple quantification of the MC. The MC may be either acutely enhanced, reduced or not changed by smoking. Long-term smoking impairs MC. The enhancement of MC by β2-agonists was very limited in most patients with CF. In the hope of increasing mucus transport in patients with CF, these are treated with various chest physiotherapy techniques. The radioaerosol based method of measurement of MC could assess mucus clearance by chest physiotherapy and cough. (au)

Ozone is a respiratory irritant that has been shown in animals to increase the premeability of the respiratory epithelium. In the study the authors have recently reported that respiratory epithelial permeability was similarly affected in eight healthy non-smoking young men exposed to ozone (ARRD, 135 (1987) 1124-8). Permeability was evaluated by determining the pulmonary clearance of inhaled aerosolized 99mTc-DTPA with sequential posterior lung imaging by a computer-assisted gamma camera. In a randomized crossover design, 16 young men were exposed for 2 h to purified air and 0.4 ppm ozone while performing intermittent high intensity treadmill exercise; forced vital capacity (FVC) was measured before and at the end of exposures. The results demonstrate that ozone exposure increased respiratory epithelial permeability. Such an increase may be a manifestation of direct ozone-induced epithelial-cell injury, lung inflammation, or both

Averages and standard deviations of 99mTc-DTPA and 131I-hippurate slope clearance were consecutively determined for 56 male Wistar rats, with a body-weight of 271 ± 69 g in a single investigation. Clearance of 99mTc-DTPA was 17.4 ± 3.4, that of 131I-hippurate was 34.3 ± 7.2 μl · s-1 per 100 g body weight. For 17 rats inulin and PAH clearances were determined after 3 days with the steady-state method with continuous infusion and 3-4 periods of urine collection. During the same periods endogeneous creatinine clearance was determined. 99mTc-DTPA slope clearance correlated well with inulin clearance, also the hippurate with the PAH clearance. The high values of the filtration fraction, calculated from radioisotope and chemical methods, and the low PAH extraction of 42% lead to the conclusion, that PAH and hippurate are incompletely eliminated by the rat kidney from plasma and therefore are inadequate for determining renal blood flow in rats. Creatinine clearance was 4.7 ± 1.38 μl · s-1 per 100 g body weight, much lower than that of inulin and 99mTc-DTPA. Therefore is assumed, that tubular reabsorption of creatinine occurs and creatinine clearance cannot serve for the evaluation of GFR in rats. For this, however, the clearance of 99mTc-DTPA seems well applicable in Wistar rats. (author)

Gamma imaging was used to measure the rate of clearance of aerosolized 99mTc-human serum albumin (HSA) from the lungs of control guinea pigs and guinea pigs that received increased lung inflation or lung injury. Anesthetized guinea pigs were ventilated for 6 min with an aerosol of HSA and the radioactivity in the chest was monitored for 2 h with a gamma camera to determine whether the clearance rate would be a reliable assessment of lung epithelial permeability. Increased lung volumes were effected by application of 5 or 7 cm H2O positive end-expired pressure (5-PEEP and 7-PEEP, respectively). Lung injury was induced either by intravenous oleic acid (OA, 27-73 μl/kg) or inhalation of nitrogen dioxide (NO2, 80-100 ppm) for 2 h. Postmortem extravascular lung water volume (EVLW) provided an assessment of the degree of lung injury. Tracer clearance rates in animals receiving 5 or 7 cm H2O PEEP were not significantly different from controls (K = 0.15 ± 0.05 and 0.24 ± 0.10 vs 0.12 ± 0.03%/min, respectively, p > .05). Animals exposed to NO2 had faster tracer clearance rates (K = 0.33 ± 0.21%/min, p 2-exposed guinea pigs correlated well with injury as assessed by EVLW (r = .93, p 2O PEEP (K = 0.58 ± 0.41%/min, EVLW = 8.1 ± 0.8 mL/g dry lung tissue, p < .05), but there was no correlation between these parameters in this injury model. It is concluded that imaging of the disappearance of radiolabeled HSA in the guinea pig can be a useful index of lung epithelial permeability, but this technique is limited to certain models of lung injury. 33 refs

Order of magnitude and standard deviation of 99mTc-DTPA and 131I-hippurate slope clearance were analyzed successively in 56 male Wistar rats. The clearance of 99mTc-DTPA was 17.4 ± 3.43 μl · s-1 (100 g b-w)-1, of 131I-hippurate 34.3 ± 7.21 μl · s-1 (100 g b-w)-1. In 17 rats inulin and PAH clearances were analyzed by steady state method with permanent infusion and 3 to 4 urine collection periods 3 days later. The endogeneous creatinine clearance was determined within the same periods. The 99mTc-DTPA slope clearance corresponded to the inulin clearance, as well as the hippurate clearance to the PAH clearance. The high filtration fraction calculated from nuclear medicine and chemical clearance methods and the low PAH extraction (42%) let suggest that PAH and hippurate are eliminated only incompletely from plasma in rat kidney and are unsuitable for determination of renal blood supply in rats. The creatinine clearance with 4.7 ± 1.38 μl · s-1 (100 g b-w)-1 was far beneath the clearance of inulin and 99mTc-DTPA, supposing that creatinine is reabsorbed tubularly in part and the creatinine clearance can not be used for valuation of the GFR in rats. However, for this the 99mTc-DTPA clearance in Wistar rats seems to be well suited. (author)

Various methods to determine hepatic function have been studied, and among these, calculated maximal removal rate of ICG (ICG R-max) is more accurate and sensitive index for quantification of hepatic function. But calculation of ICG R-max is time-consuming, invasive, and expensive study, and even ICG R-max 1 day study is still complicated. So we tried to evaluated of hepatic function test using 99mTc-DISIDA plasma clearance rate. The author studied 11 cases of normal control, 4 cases of acute hepatitis, 8 cases of chronic hepatitis, and 19 cases of liver cirrhosis. The results were as follows: 1. In normal control, DISIDA-K was 0.70 min-1, in liver cirrhosis 0.25 min-1, in acute hepatitis 0.46 min-1, and in chronic hepatitis 0.14min-1. The most severe depressed DISIDA-K value was observed in liver cirrhosis. 2. Comparison of DISIDA-K value to liver function indices revealed no correlation between DISIDA-K value and serum albumin, prothrombin time, total bilirubin, SGOT, and alkaline phosphatase. 3. DISIDA-K value in liver cirrhosis with complication such as ascites, splenomegaly, esophageal varices, and hepatic coma was more decreased than without complication. With the above result, calculation of DISIDA-K value was found easily available, accurate, and simple index for quantification of hepatic function.

Full Text Available Abstract Background Clearance of inhaled technetium-labeled diethylenetriamine pentaacetate (99mTc-DTPA is a marker of epithelial damage and an index of lung epithelial permeability. The aim of this study was to investigate the role of 99mTc-DTPA scan in patients with Idiopathic Pulmonary Fibrosis (IPF. Our hypothesis is that the rate of pulmonary 99mTc-DTPA clearance could be associated with extent of High Resolution Computed Tomography (HRCT abnormalities, cell differential of bronchoalveolar lavage fluid (BALF and pulmonary function tests (PFTs in patients with IPF. Methods We studied prospectively 18 patients (14 male, 4 female of median age 67yr (range 55–81 with histologically proven IPF. HRCT scoring included the mean values of extent of disease. Mean values of these percentages represented the Total Interstitial Disease Score (TID. DTPA clearance was analyzed according to a dynamic study using a Venticis II radioaerosol delivery system. Results The mean (SD TID score was 36 ± 12%, 3 patients had mild, 11 moderate and 4 severe TID. Abnormal DTPA clearance half-time (t1/2 Conclusion Our data suggest that 99mTc-DTPA lung scan is not well associated with HRCT abnormalities, PFTs, and BALF cellularity in patients with IPF. Further studies in large scale of patients are needed to define the role of this technique in pulmonary fibrosis.

To investigate the relationships between the respiratory epithelial clearance of micronic aerosolized /sup 99m/Tc-DTPA (RC-DTPA) and pulmonary function, serum angiotensin-converting enzyme (SACE), and lymphocytic alveolitis in patients with sarcoidosis, RC-DTPA was measured in 49 nonsmokers with pulmonary sarcoidosis and 38 normal nonsmokers. Pulmonary involvement was evaluated on chest roentgenograms (type O = normal, type I = hilar adenopathies, type II = hilar adenopathies associated with parenchymal shadows, type III = parenchymal shadows without adenopathy) and by pulmonary function tests. Serum angiotensin-converting enzyme was determined, and a bronchoalveolar lavage was performed for alveolar lymphocyte differential counting (Ly%). RC-DTPA was increased (greater than or equal to 1.96%/min) in 12 of 31 patients with type II or III involvement but was normal in all 18 patients with type O or I involvement (p = 0.002). Patients with increased RC-DTPA had low FVC, TLC, FEV1, and resting Pao2 (p less than 0.05); resting and exercise AaPo2 were increased (p less than 0.05), but RC-DTPA correlated negatively with FEV1 (p less than 0.01), Pao2 at rest (p less than 0.005), and DLCO (p less than 0.05) and positively with resting and exercise AaPO2 (p less than 0.01). In patients with increased RC-DTPA (42 +/- 17%), Ly% did not differ from Ly% in patients with normal RC-DTPA (34 +/- 16%). SACE was increased in patients with increased RC-DTPA (56 +/- 26 U/ml versus 38 +/- 16 U/ml; p = 0.007) and correlated positively with RC-DTPA (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

We measured pulmonary epithelial permeability by 99mTc-DTPA radioaerosol clearance in patients with diabetes and correlated with the presence of microangiopathy to understand the pathophysiology of pulmonary microangiopathy and evaluate 99mTc-DTPA radioaerosol clearance as a diagnostic test to assess pulmonary microangiopathy. We performed 99mTc-DTPA radioaerosol scan in 10 normal subjects, 10 asymptomatic smokers, 20 diabetic patients without history of smoking (10 with microangiopathy, 10 without microangiopathy). 99mTc-DTPA clearance half-time (T1/2) was calculated, then compared with the result of chest radiography and pulmonary function test. Chest radiography and pulmonary function test were normal in all subjects. There were no significant difference of clinical or laboratory characteristics between these groups except age. The diabetic patients with microangiophaty were significantly older (p1/2 of normal subjects and asymptomatic smokers were significantly different (65.2±23.7 min vs 39.6±9.8 min, p1/2 was 90.5±46.5 min and significantly delayed when compared with those of normals and asymptomatic smokers (p1/2 of diabetic patients without microangiopathy, 70.0±12.7 min, was not significantly different from those of normals or asymptomatic smokers (p>0.05). No significant correlation was found between the T1/2 and spirometric parameters including DLco, FVC, FEV1, FEV1/FVC (%) and FEF25-75% in all subjects, and between the T1/2 and duration of diabetes in diabetic patients. Eventhough the influence of age can't be excluded, delayed 99mTc-DTPA clearance half-time (T1/2) in diabetic patients with microangiopathy indicates decreased pulmonary capillary permeability as one of the pathophysiologic results of pulmonary microangiopaththy. Further studies are needed in larger number of age matched control and diabetic patients to evaluate the diagnostic efficacy

With recent technical advances in aerosol technology, the study of regional ventilation using [/sup 99m/Tc]DTPA aerosol has become increasingly popular. Using a cascade impactor, the authors have assessed droplet size distribution from a newly designed nebulizer. Delivery efficiency of [/sup 99m/Tc]DTPA aerosol to normal subjects was improved 70% with a 10% concentration of ethanol in the nebulizer. Using filter paper fixed to the delivery end of the aerosol device, and varying ethanol concentrations from 0-10%, an 87% increase of deposited radioactivity is measured. The addition of ethanol did not alter clearance characteristics of [/sup 99m/Tc]DTPA from the lung nor did it affect droplet size distribution

Technetium-99m aerosol lung clearance has been used as a means to evaluate pulmonary-alveolar capillary integrity. Impairment has been demonstrated in conditions such as interstitial lung disease and by active cigarette smoking. The effects of passive smoking have not been well documented. Sixteen volunteers underwent aerosol lung clearance studies with estimation of half clearance times before and immediately following exposure to cigarette smoke. Formal lung function studies, plasma nicotine levels and ambient carbon monoxide levels within the smoke chamber were estimated on both occasions. These results were compared with paired aerosol studies performed on 20 subjects acting as controls. Aerosol clearance was performed via a commercially available system (Ultravent), charged with 1 GBq99mTc DTPA. Aerosol was inhaled for five minutes, with normal tidal breathing, followed by washout for 35 minutes. Thirty-second frames were collected into a 64 x 64 word matrix. A cine was displayed to review movement and position of the stomach. Regions of interest were drawn to allow for these. An exponential fit was applied to the period before the movement was noted. It was noted that movement during the time of data acquisition may cause altered clearance time; similarly, swallowed activity in the oesophagus and stomach may be significant. After correcting for the above, no statistically significant change in aerosol lung half clearance time was demonstrated with passive smoking. 9 refs., 9 figs

Pulmonary emboli lead to regional limitation of pulmonary artery perfusion, often without affecting distribution of ventilation. We have studied the effect of this regional reduction of pulmonary artery perfusion on the integrity of epithelium of alveoli (and possibly bronchioli). Integrity of alveolar epithelium was assessed by measuring regional rates of clearance from lung to blood of an inhaled aerosol of a small molecular weight solute, sup(99m)Tc DTPA (technetium-99m diethylene-triamine-penta-acetate). Ten patients with pulmonary emboli were studied, where the diagnosis was made from 'mismatching' seen on ventilation (V) and perfusion (Q) lung scintigraphy. Rates of clearance of DTPA in regions with normal V/Q ratios were compared with embolized regions with high V/Q ratios. Clearance rates were increased in embolized regions (V/Q ratio > 1) : 2.59 +- (SD) 0.89%. min-1, compared with normal regions (V/Q ratio -1 (p<0.01). In repeat studies in nine patients (one died), after intervals between 2 and 12 weeks, the V/Q ratio of previously embolized regions decreased towards unity in all nine patients, suggesting resolution. The differences in clearance rates for DTPA between normal and embolized regions decreased in association with this return towards normal of V/Q ratios. We surmise that reduction in pulmonary artery perfusion which occurs in pulmonary embolic disease alters the integrity of the alveolar (and possibly bronchiolar) epithelium. This effect is largely reversible, recovering with return of pulmonary artery perfusion

Objectives Glomerular filtration rate can be measured as the plasma clearance (CL) of a glomerular filtration rate marker despite body fluid disturbances using numerous, prolonged time samples. We desire a simplified technique without compromised accuracy and precision. Materials and methods We compared CL values derived from two plasma concentration curve area methods – (a) biexponential fitting [CL (E2)] and (b) Tikhonov adaptively regularized gamma variate fitting [CL (Tk-GV)] – for 4 versus 8 h time samplings from 412 99mTc-DTPA studies in 142 patients, mostly paediatric patients, with suspected fluid disturbances. Results CL (Tk-GV) from four samples/4 h and from nine samples/8 h, both accurately and precisely agreed with the standard, which was taken to be nine samples/8 h CL from (noncompartmental) numerical integration [CL (NI)]. The E2 method, four samples/4 h, and nine samples/8 h median CL values significantly overestimated the CL (NI) values by 4.9 and 3.8%, respectively. Conclusion Compared with the standard, CL (E2) from four samples/4 h and from nine samples/8 h proved to be the most inaccurate and imprecise method examined, and can be replaced by better methods for calculating CL. The CL (Tk-GV) can be used to reduce sampling time in half from 8 to 4 h and from nine to four samples for a precise and accurate, yet more easily tolerated and simplified test. PMID:26465802

The capacity of separated kidney function, estimated by means of 131I- or 123I-hippurate clearance, was compared with the capacity results from 99mTC-DMSA scintigraphy. There was found a good correlation (0.98) of the two methods. In patients with urine congestion the frequent high capacity in hippurate clearance in comparison to DMSA-scintigraphy on the affected kidney was evident. This results needs further investigations. In cases where it is necessary to evaluate the relative separated capacity of both sides, the hippurate clearance can be substituted by combination of DMSA-scintigraphy and isotope renogram. Considering surgical consequences, it is important to carry out both methods. (orig.)

As an index of permeability of the alveolar epithelium, the clearance of an inhaled aerosol of /sup 99m/Tc-DTPA is increased in several disease states. However, the usefulness of the test to assess the severity of disease is limited because healthy smokers also have abnormally rapid rates of clearance. Because the stability of the /sup 99m/Tc-DTPA bond might be a contributory factor, we tested the affinity of /sup 99m/Tc for DTPA in vitro, and in groups of healthy smokers (n = 13) and nonsmokers (n = 7) we measured the clearances of /sup 99m/Tc-DTPA and /sup 113m/In-DTPA, which have a similar molecular shape and charge. In vitro, sodium hypochlorite or hydrogen peroxide released as much as 98% of free /sup 99m/Tc from the /sup 99m/Tc-DTPA complex. When incubated with human neutrophils stimulated with phorbol myristate acetate, between 4 and 7% of free /sup 99m/Tc-DTPA was released after 30 min, and 12% was released after 60 min. In vivo, the clearances of both /sup 99m/Tc-DTPA and /sup 113m/In-DTPA in the smokers (n = 13) were faster than in the nonsmokers (n = 7) (p less than 0.05). Within the smokers, the mean /sup 99m/Tc-DTPA clearance (T1/2 25 +/- 4 min) was faster than the mean /sup 113m/In-DTPA clearance (34 +/- 6 min), (p less than 0.05). For nonsmokers, the difference was smaller (T1/2 /sup 99m/Tc-DTPA, 56 +/- 6; T1/2 /sup 113m/In-DTPA, 62 +/- 6) and not significant. During hyperinflation, smokers (n = 8) and nonsmokers (n = 8) both demonstrated an increase in /sup 113m/In-DTPA clearance.

Sequential changes in the regional distribution of technetium 99m Teboroxime (SQ30217) were evaluated in nine dogs with graded coronary artery stenosis, occlusion and reperfusion of either the left anterior descending or left circumflex arteries. 99mTc-Teboroxime accumulation recorded by planar imaging was compared with direcly measured coronary blood flow (Doppler) and regional myocardial perfusion (microspheres). Serial images were recorded beginning at the time of injection and continuing for the next 18 min. The data were summed from minutes 2-3, 3-6, 4-8 and 9-18 after injection for comparison with the other parameters. Myocardial clearance of Teboroxime was analysed at each level of blood flow. There was a linear relationship between the Teboroxime activity ratio (abnormal/normal) and coronary blood flow (r=0.96) and regional myocardial perfusion (r=0.99). Zones of diminished perfusion were least apparent in the summed images recorded during minutes 2-3. In later images, the lesions were well visualized. The myocardial clearance half-times at 100%, 75% and 50% flow were not significantly different, while clearance half-time at total occlusion was significantly (P<0.01) faster. In the 3-6, 4-8 and 9-18 minutes summed images, the Teboroxime activity ratio increased significantly (P<0.01) after reperfusion compared with total occlusion. (orig.)

Determination of the plasma (ClPl) and specific hepatic clearance (ClHp) of 99mTc-HEPIDA is gaining acceptance as one of the best tests for the assessment of liver parenchyma functional capacity. A standard method utilises numerous blood samples,collected after injection of the radiopharmaceutical, plus collection of the urine if specific hepatic clearance is required. It is not always necessary to obtain values of the clearances by means of the laborious multi-sample procedure. In the paper there are presented formulas,based on experimental data, that form the basis of a simplified method for determination of ClPl and ClHp using single administration of 99mTc-HEPIDA. To arrive at the value of ClPl it is sufficient to withdraw 1 blood sample in the time range of 60 to 83 min post administration of the radio-pharmaceutical. If ClHp is required, additional collection of urine over the time from 0 to 88-100 min post injection is necessary. The values of ClPl and ClHp obtained by the simplified procedure are in full accordance with those obtained by the reference method utilising a series of blood samples, collected from 5 to 90 min post injection. The simplified method is sufficient as a procedure for screening of patients for liver parenchymal damage. (author)

This report describes the evaluation of a series of novel cationic {sup 99m}Tc-nitrido complexes, [{sup 99m}TcN(DTC)(PNP)]{sup +} (DTC=crown ether-containing dithiocarbamates; PNP=bisphosphine), as potential radiotracers for myocardial perfusion imaging. Synthesis of cationic {sup 99m}Tc-nitrido complexes was accomplished in two steps according to literature methods. Biodistribution studies were performed in rats. Planar images of Sprague-Dawley rats administered with 15{+-}2 MBq of cationic {sup 99m}Tc radiotracer were obtained using a PhoGama large field-of-view Anger camera. Samples from both urine and feces were analyzed by a reversed-phase radio-HPLC method. Results from biodistribution studies showed that most of the cationic {sup 99m}Tc-nitrido complexes have a high initial heart uptake with a long myocardial retention. They also show a rapid clearance from the liver and lungs. Cationic complexes [{sup 99m}TcN(L2)(L6)]{sup +} and [{sup 99m}TcN(L4)(L6)]{sup +} show heart/liver ratios four to five times better than that of {sup 99m}Tc-sestamibi due to their much faster liver clearance. Their heart uptake and heart/liver ratio are comparable to that of {sup 99m}TcN-DBODC5 within the experimental error. These findings have been confirmed by the results from imaging studies. Radio-HPLC analysis of urine and feces samples indicated that there was very little metabolism of cationic {sup 99m}Tc-nitrido complexes in rats under anesthesia. The key finding of this study is that lipophilicity remains the most important factor affecting both heart uptake and target-to-background (T/B) ratios. Crown ethers are very useful functional groups to improve the liver clearance of cationic {sup 99m}Tc-nitrido complexes. It is the combination of the appropriate DTCs and bisphosphines that results in cationic {sup 99m}Tc-nitrido complexes with high heart uptake and fast clearance from the liver at the same time. The fast liver clearance of [{sup 99m}TcN(L2)(L6)]{sup +} and [{sup 99

The main purpose of this study has been introduction of a new method for alveoli-capillary permeability evaluation. Many reports pointed out to the altered transit of soluble particles through this barrier. From pathophysiological aspect the main interest is the elucidation of permeability's alteration in different pulmonary pathology. We decided to use for lung epithelial permeability measurements 99mTc-DTPA inhaled aerosols and sequential assessment of its lung clearance. The aerosols were obtained using oxygen flow nebulizers with aerosols' generators Ultra Vent (Malinkrodt) and Venticis II (CIS bio international) that enabled as to get submicron particles. Oxygen flow between 9 and 11 liters per minute was used. Optimum images were obtained with 1480 MBq of inhaled aerosols at least 2 to 3 minutes. DTPA that was used for aerosols labeling had been produced in our Department and the results were compared with DTPA provided by CIS bio international. High correlation between both agents was proven. During the whole study ex tamper prepared radiopharmaceuticals were used and quality control was done using paper chromatography method. Acquisition was done in sitting position with gamma camera interfaced to a ADAC and Scintiview. The measurements lasted for 20 minutes. Data were stored on 64x64 matrices. Regions of interest over both lungs were drown and each one was divided in three segments: apical, medial, and basal. Using computer program curves of 99mTc-DTPA lung clearance were derived. From the obtained time activity curves half-time of the global and the regional lung clearance was assessed. In the control group comprised of 32 healthy volunteers (non-smokers) we had got values, used after works as reference range. Our normal values for global clearance are: 68±5,5 min. for left whole lung, 68,1±6,5 min for right whole lung, and 49±7,7 min for apical, 66,9±8 min for middle, and 75,9±6,4 min basal regional lung clearance, and they are in keeping with the

The mechanisms of dyspnea and exercise intolerance have not been fully elucidated. We aimed to investigate the clearance rate of technetium-99m diethyltriaminepentaaceticacid (Tc-99m DTPA) from lungs in hyperthyroid patients without clinical evidence of lung disease and to explore the interactions between their Tc-99m DTPA radioaerosol lung scintigraphy, spirometric measurements, and the levels of thyroid hormones. We studied 19 hyperthyroid patients and 16 sex- and age-matched controls. Thyroid hormone levels were assessed. Spirometric lung function tests, diffusing capacity of the lung for carbon monoxide (DLCO) and the clearance rate of Tc-99m DTPA were performed in all participants. Ratio of DLCO value to the alveolar ventilation (DLCO/VA) and the means of half-time (T1/2) of Tc-99m DTPA clearance rate, which were used to evaluate alveolar-capillary membrane permeability, were calculated. There were no statistical differences between spirometric parameters (vital capacity (VC), force vital capacity (FVC), one second forced expiratory volume (FEV1)/FVC, mean forced expiratory flow during the middle of FVC (FEF 25-75)) of the two groups (p>0.05). Although the mean FEV1 level was significantly lower in the hyperthyroid patients than the control subjects (p1 was only less than 80 percent of the predicted value. No significant difference in the means of DLCO, DLCO/VA or T1/2 values of Tc-99m DTPA clearance was observed between the two groups (p>0.05). In hyperthyroid patients, there was a positive relation between DLCO/VA, DLCO/VA% and T1/2 values of Tc-99m DTPA clearance (p1/2 values of Tc-99m DTPA clearance in hyperthyroid group (p>0.05). We conclude that increased thyroid hormones have no effect on permeability of alveolar-capillary membrane in hyperthyroid patients. (author)

Parameters affecting the hepatobiliary clearance of /sup 99m/Tc N(2,6-dimethylphenylcarbamoylmethyl) iminodiacetic acid (Tc-HIDA) were evaluated in dogs. Competitive clearance studies were performed with Tc-HIDA after infusion to plasma saturation levels of an anion, sodium sulfobromophthalein (BSP), and a cation, oxyphenonium. The results demonstrated that Tc-HIDA is transported through hepatocytes by a carrier-mediated organic-anion pathway. The data are consistent with an alteration of the elimination kinetics of Tc-HIDA induced by elevations in the serum bilirubin level, and it is predicted that serum bilirubin at some increased concentration will dominate the distribution and elimination kinetics of Tc-HIDA independently of hepatobiliary status. A quantitative description of liver function in terms of regional distribution and elimination rate constants will require either a pharmacokinetic model that expressly includes the effects of bilirubin from transport binding sites, or the development of new hepatobiliary agents that use a different clearance mechanism from that used by bilirubin

quality of a commercial [99mTc]DTPA preparation (C.I.S., France) with reference to stability, protein binding and accuracy of the determined plasma clearance values as a measure of GFR. The stability of the preparations was studied by thin-layer chromatography, the in vitro protein binding by Sephadex...... filtration after incubation with human serum albumin and in vivo protein binding by filtration of human plasma. The accuracy of the plasma clearance values was investigated by comparison with the simultaneously measured plasma clearance of [51Cr]EDTA. There was no detectable free pertechnetate or hydrolysed...... reduced technetium in eight vials five and six hours after the preparation. The in vitro protein binding 10 (20), 120 and 300 min after the preparation of eight vials was 2.3% (0.8%), 0.2% and 0.1%, respectively. The in vivo protein binding in 12 patients 5, 90 and 180 min after the injection was 0.3%, 0...

Biological dosimetry estimates the absorbed dose taking into account changes in biological parameters. The most used biological indicator of an exposition to ionizing radiation is the quantification of chromosomal aberrations of lymphocytes from irradiated individuals. The curves of dose versus induced biological effects, obtained through bionalyses, are used in used in retrospective evaluations of the dose, mainly in the case of accidents. In this research, a simple model for electrons and photons transports was idealized to simulate the irradiation of lymphocytes with 99m Tc, representing a system used for irradiation of blood cells. The objective of the work was to establish a curve of dose versus frequencies of chromosomal aberrations in lymphocytes of human blood. For the irradiation of blood samples micro spheres of human serum of albumin (HSAM) market with 99m Tc were used, allowing the irradiation of blood with different administered activities of 99m Tc, making possible the study the cytogenetical effects as a function of such activities. The conditions of irradiation in vivo using HSAM spheres marked with 99m Tc were simulated with MCNP 4C (Monte Carlo N-Particle) code to obtain the dose-response curve. Soft tissue composition was employed to simulate blood tissue and the analyses of the curve of dose versus biological effect showed a linear quadratic response of the unstable chromosomal aberrations. As a result, the response of dose versus chromosomal aberrations of blood irradiation with 99m Tc was best fitted by the curve Y=(8,99 ±2,06) x 1--4 + (1,24 ±0,62) x 10-2 D + (5,67 ± 0,64) x 10-2 D2. (author)

For evaluation of technetium-99m dimercaptosuccinic acid (99mTc-DMSA) renal uptake as an absolute renal function, 99mTc-DMSA uptake was compared with endogenous creatinine clearance (Ccr) in gentamicin-induced nephrotoxicity. Gentamicin (40 mg/kg/day) was given subcutaneously to male Wistar rats for periods of 3, 6, 9 and 12 days. On the next day, the renoscintigraphy was performed 2 hours following intravenous injection of 99mTc-DMSA and Ccr was measured. On the 7th day, 99mTc-DMSA uptake was significantly lower in the treated rats than that in control (32.27±0.92 vs 39.84±2.24%; p99mTc-DMSA uptake was measured and the histological examination was done. On the 4th day, 99mTc-DMSA uptake was significantly lower than that on the 1st day (32.32±3.00 vs 38.91±1.95%; p99mTc-DMSA uptake reduces earlier than Ccr in gentamicin-induced nephrotoxicity and 99mTc-DMSA uptake is a reliable indicator in the evaluation of a renal function in drug-induced nephrotoxicity. (author)

The objective of this study was to develop an equation to predict dual plasma sample method (DPSM) 99mTc-diethylene triamine pentaacetic acid (99mTc-DTPA) plasma clearance from single plasma sample method (SPSM), and to clarify the condition in which DPSM can be substituted by SPSM in measurement of glomerular filtration rate (GFR). Patients with chronic kidney disease (CKD) were selected. Watson modified Christensen and Groth equation was used to calculate 99mTc-DTPA plasma clearance by SPSM (sGFR). The equation recommended by the Nephrourology Committee of the Society of Nuclear Medicine was used to calculate 99mTc-DTPA plasma clearance by DPSM (tGFR) in each patient. The difference between sGFR and tGFR was expressed as percent of the average of these two methods, and tGFR was predicted from sGFR. Plasma creatinine was measured by the kinetic picrate method, and GFR estimated by abbreviated modification of diet in renal disease (MDRD) equation (aGFR) and Cockcroft-Gault equation (cGFR) were evaluated as criteria in selection of DPSM and SPSM. Three hundred and sixty-nine patients with CKD were selected (208 male and 161 female). The average age and body weight were 51.4±15.5 years and 67.2±12.5 kg, respectively. The causes of CKD were glomerular disease, renal arterial stenosis, chronic tubulointerstitial disease, and other causes or causes unknown. The average tGFR was 62.9±36.5 ml/min/1.73 m2, ranging from 1-180 ml/min/1.73 m2. sGFR was significantly correlated with tGFR (r=0.9194, p2; in contrast, then tGFR was±30 ml/min/1.73 m2, the difference was constant (-1.1%, 95% confidence interval -18.3%, 16.1%), and tGFR could be predicted from sGFR using the equation: predicted tGFR (ml/min/1.73 m2)=7 4244+0.7318 x sGFR+0.0022 x sGFR2 (n=299, r2=0.9428, p2, the diagnostic sensitivity of a cut off value of aGFR=45 ml/min/1.73 m2 was 91.8%, and recommended as a criterion in the selection of DPSM and SPSM. When GFR ≥30 ml/min/1.73 m2, tGFR can be predicted from s

A new analytical method was developed for sup(99m)Tc-N-pyridoxy1-5-methyltryptophan (sup(99m)Tc-PMT) dynamic curves in the heart and liver using computer. Four parameters were obtained: sup(99m)Tc-PMT disappearance rate from plasma (Kd), hepatic uptake rate (Ku), hepatic excretion rate (Ke) and peak time of hepatic uptake-excretion curve (Peak Time). These parameters were determined in 51 patients with or without liver diseases. Kd, Ku and Ke significantly decreased and Peak Time also significantly prolonged in patients with chronic hepatitis, compensated and decompensated liver cirrhosis in serial order. In patients with acute hepatitis, marked decrease of Ke was observed. A good correlation was found between these parameters and other hepatic function tests such as ALP, ChE, Albumin, γ-globulin and ICG retention test. These results suggest that parameters obtained are sensitive index for evaluating the severity of liver damage. Therefore it is considered that the computer analysis of sup(99m)Tc-PMT dynamic curves is clinically very useful as hepatic function test. (author)

Aim of this study is to determine the relationship between 51Cr-EDTA and 99mTc-DTPA slope clearance applying the 'one-compartment model'. Methods: The 'one-compartment model' was chosen to calculate and to compare the glomerular filtration rates of 25 patients with normal and pathological creatinin values after injection of 51Cr-EDTA and 99mTc-DTPA simultaneously. Results: The two clearance values correlated well (r=0.996), and the 99mTc-DTPA clearance was systematically higher (28%). The 99mTc-DTPA was calculated and compared after taking three plasma samples. Taking two samples, only minor differences were seen and the correlation was high (r=0.992). Conclusion: The results of this study encouraged us to adopt the use of 99mTc-DTPA instead of 51Cr-EDTA in determining the glomerular filtration applying the 'one-compartment model' in slope with two plasma samples. (orig.)

We present a method for estimating 99mTc-MAG3 clearance from both a single injection and two blood samples that is valid for both adults and children. It was obtained by fitting a scaled two-compartment model (having only two adjustable parameters) to adult and pediatric data from multiple centers

Aim: Real function is usually determined by means of creatinine-clearance, and of serum Cystatin C, the latter with increasing frequency. The present study analyses, whether the diagnostic accuracy of 99mTc-MAG3 clearance is comparable to that of these modern serologic methods. Patients, methods: 71 consecutive adult Caucasian patients (42 female, 29 male; age 50±16 yrs., range 20-83) who were referred to a nuclear medicine department for determination of bilateral renal function with 99mTc-MAG3 were included. Following sufficient hydration, 10 ml of blood were taken for determination of Cystatin C and creatinine in serum prior to i.v. injection of the radiotracer. According to the recommendations of the National Kidney Foundation, glomerular filtration rate (GFR) was calculated form serum creatinine using either Cockcroft and Gault and Modification of Diet in Renal Disease (MDRD) study equation. These estimates of GFR served as reference. Cystatin C is a low molecular protein produced by all nuclear cells and is eliminated to 85% by glomerular filtration. Analysis of 99mTc-MAG3 clearance was performed by means of Bubeck's formula. Results: Linear regression analysis produced Pearson's correlation coefficients of r=0.68 and r=-0.69 for the comparison of either Cystatin C and 99mTc-MAG3 clearance with the Cockcroft and Gault equation. The comparison of Cystatin C and 99mTc-MAG3 clearance with MDRD study equation resulted in correlation coefficients of r=0.755 and r=-0.77. None of these differences were significant. The exclusion of renal impairment or the detection of an at least moderate renal impairment revealed again no significant differences between Cystatin C and 99mTc-MAG3 clearance. Conclusions: Cystatin C and 99mTc-MAG3 clearance are equally suited to exclude renal impairment or to detect a relevant renal impairment. Differences between both procedures are more likely a result of the applied reference method. (orig.)

Biological dosimetry estimates the absorbed dose taking into account changes in biological parameters. The most used biological indicator of an exposition to ionizing radiation is the quantification of chromosomal aberrations of lymphocytes from irradiated individuals. The curves of dose versus induced biological effects, obtained through bionalyses, are used in used in retrospective evaluations of the dose, mainly in the case of accidents. In this research, a simple model for electrons and photons transports was idealized to simulate the irradiation of lymphocytes with {sup 99m} Tc, representing a system used for irradiation of blood cells. The objective of the work was to establish a curve of dose versus frequencies of chromosomal aberrations in lymphocytes of human blood. For the irradiation of blood samples micro spheres of human serum of albumin (HSAM) market with {sup 99m} Tc were used, allowing the irradiation of blood with different administered activities of {sup 99m} Tc, making possible the study the cytogenetical effects as a function of such activities. The conditions of irradiation in vivo using HSAM spheres marked with {sup 99m} Tc were simulated with MCNP 4C (Monte Carlo N-Particle) code to obtain the dose-response curve. Soft tissue composition was employed to simulate blood tissue and the analyses of the curve of dose versus biological effect showed a linear quadratic response of the unstable chromosomal aberrations. As a result, the response of dose versus chromosomal aberrations of blood irradiation with {sup 99m} Tc was best fitted by the curve Y=(8,99 {+-}2,06) x 1-{sup -4} + (1,24 {+-}0,62) x 10{sup -2} D + (5,67 {+-} 0,64) x 10{sup -2} D{sup 2}. (author)

This study was a comparison of the Bubeck and Russell (1996) methods, both of which are used to calculate 99mTc-MAG3 plasma clearance by single blood sampling in consideration of the distribution volume of patients. Quadratic polynominal approximation showed a strong correlation between the plasma clearance values obtained by the two methods. The quantitative values obtained by the Bubeck method tended to be lower than those obtained by the Russell (1996) method in the high clearance range. However, in the low to medium clearance range (below 250 ml/min/1.73 m2), there was almost no difference between the values, and the relationship between the values obtained by the two methods could be expressed by a straight regression line. A comparison of plasma clearance values according to difference in blood sampling time (35 min and 44 min sampling) in adults showed that there was no significant change in clearance regardless of the state of renal function. Correlation of the renal uptake rate obtained by the Bubeck method using a gamma camera could be expressed by a good straight regression line that passed around the origin of the coordinates. The results showed that, although the plasma clearance values obtained by the Bubeck method tended to be underestimated in the high clearance range compared with the values obtained by the Russell (1996) method, there was a very good correlation between the values obtained by the Bubeck method and renal uptake rate. (author)

To correlate Gates glomerular filtration rate (GGFR) using technetium-99m diethylene triaminepentacetic acid (99mTc DTPA) with 24-hour creatinine clearance (CRCL) and to establish relationship with duration of diabetes in patients with early diabetic nephropathy. Study Design: A cross-sectional comparative study carried out in Nuclear Medical Centre from Aug 2009 to Jan 2010 at Armed Forces Institute of Pathology (AFIP), Rawalpindi, Pakistan. Patients and Methods: A total of eighty three subjects were enrolled, who were divided into three groups; group 1 comprised 31 normotensive diabetics, group 2 had 37 hypertensive diabetics while group 3 had 15 normal subjects. The DTPA GFR and creatinine clearance in healthy subjects as well as diabetic patients were compared using the unpaired student's t-test. The linear association between GFR, creatinine clearance and disease duration was expressed by Pearson's correlation coefficient 'r' along with their significance levels. Results: Gates GFR showed hyperfiltration in normotensive diabetics (96.6 +- 3.3 ml/min/1.73 m/sub 2/), significantly (p<0.05) higher than controls (85.5 +- 5 ml/min/1.73 m/sub 2/), whereas hypertensive diabetics had a significantly lower (p<0.05) Gates GFR (76.8 +- 3.7) than that of controls. Significant degree of correlation existed between GGFR and CRCL in hypertensive diabetics (p<0.05, r=0.716) and controls (r=0.546). Gates GFR also showed good correlation with duration of diabetes in both diabetic groups as compared to that of CRCL. GGFR also correlated well with duration of hypertension 0.37 (0.31-0.43) as compared to CRCL 0.155 (0.15-0.16) in all groups. Conclusions: The 99mTc-DTPA clearance correlates significantly with 24-hour creatinine clearance as well as with disease duration and can provide a simple and convenient index of kidney function in patients of early diabetic nephropathy. (author)

Mucocoiliary clearance of respiratory channels is one of the important mechanisms guarding against retention of foreign particles within the lungs. Disorders of the mucociliary transport system play a major role among non-respiratory function in causing congenital and acquired bronchial disease. Thus, objective assay of the system is essential to recognizing and understanding abnormalities. In the present paper, a simple, noninvasive, and reliable in vivo method of monitoring mucociliary clearance function is reported. 18 healthy subjects and 32 COPD patients were studied with 99mTc-DTPA aerosol scintigraphy. Monitoring was performed by visual inspection (cinescintigraphy, to observe the distribution of 99mTc-DTPA particles and the movement of radiomucous 'hot bolus') and quantitative analysis (two indexes were utilized: the first is airway clearance ratio (ACR); the second is mucociliary clearance rate (MCC), i.e. speed of advances of mucous bolus, calculated reported by Zwas). Siemens 3700 SPECT, 64 X 64 byte mode, zoom 2. Sequential images (frame/60s) were obtained for 120 minutes. The deposition pattern of 99mTc-DTPA particles in normal subjects was uniform. The deposition pattern in COPD patients demonstrated in general a centrally located distribution with major retention in the proximal airways. Four abnormal mucous transport patterns were regionally observed: stasis, regurgitation, straying and spiral or zigzag transport. Statistical analysis showed there was a significant difference of ACR between healthy subjects and COPD patients at different time points (P<0.05). The MCC in healthy subjects and COPD patients was 3.89±0.92 mm/min and 1.32±0.59 mm/min respectively. The method of assaying tracheo-bronchial mucociliary clearance reported here is simple and objective. It has not only the advantage of visual inspection and quantitative analysis, but also has a potential usefulness in studying other bronchial diseases and evaluating of therapeutic

The clearance of Tc99m-DTPA aerosols from the lung has been used to detect and quantitate alterations in the permeability of the pulmonary epithelium. Clearance of the radionuclide is accelerated by both chronic and acute injuries to the lung and by smoking. Several laboratories have reported that Tc99m-DTPA clearance from upper lobes exceeded that from lower lobes in upright subjects. To investigate this phenomenon further the authors studied subjects with simultaneous anterior and posterior cameras in upright and supine positions. In the upright position, clearance from both the anterior and posterior upper regions of interest (ROI's) exceeded the lower regions (-1.64 +- .42 S.D. vs. -0.75 +- .41, anterior, p < .05, n=6), -1.04 +- .23 vs. -0.50 +- .36, posterior. All units = %/min. This difference was not observed in the supine subjects. Clearance from the anterior chest exceeded that from the posterior chest in the supine subjects (-1.28 +- .45 vs. -0.05 +- 1.08) and a small increase in radio-activity was observed in at least one ROI of 5 of 6 subjects from the posterior camera. An increase in activity is likely to be secondary to labeling of blood pool, which would have greatest affect where pulmonary blood volume is largest. Computer processing of the entire lung without observer bias in ROI placement showed similar effects of posture over non-peripheral ROI's. Five subjects breathed on PEEP to cause airspace distention, causing clearance to double. Both dependency and airspace distention appear to influence clearance of aerosolized DTPA, the latter may occur by stretching of epithelial pores

On 32 patients with lung fibrosis of various genesis, chronically obstructive bronchitis and carcinomas the resorptive clearance of the lung in comparison to 12 normal persons was carried out, specifically with a 99mTc-pertechnate aerosol in an atomiser (particle diameter of < 1 μm) doing inspiring vital capacity manuveurs. Patients with chronically obstructive bronchitis and lung fibrosis showed a clearance which slowed down in the middle, carcinoma patients showed a strongly slowed resorptive clearance in the diseased areas. A comparison with spirometric data and gas exchange parameters brought merely for MMEF a weakly significant correlation. A decisive influence of the condition of the bronchial mucous membrane on the result of the resorptive clearance was ascertained. Pollutants remain with decreased clearance longer in the lung and could possibly increase a predisposition to cancer. By the measuring of the resorptive clearance it can at least be determined which people were exposed for longer times to the damaging effects of such materials. (TRV)

This study aims to establish molecular modeling methods for predicting the liver and kidney uptakes of Tc-99m labeled quinolone antibiotics. Some three-dimensional quantitative-activity relationships (3D-QSAR) models were developed using comparative molecular field analysis and grid-independent descriptors procedures. As a first report on 3D-QSAR modeling, the predicted liver and kidney uptakes for quinolone antibiotics were in good agreement with the experimental values. The obtained results confirm the importance of hydrophobic interactions, size and steric hindrance of antibiotic molecules in their liver uptakes, while the electrostatic interactions and hydrogen bonding ability have impressive effects on their kidney uptakes. (author)

The in vitro conversion of the lipophilic molecule [99mTc]-d,l-hexamethylpropyleneamine oxime [( 99mTc]-d,l-HM-PAO) to a hydrophilic form was studied in saline, plasma, and blood at 37 degrees C by paper chromatography and by octanol extraction. The octanol:saline ratio was 79.9. From this value...

Highly significant improvement in the pulmonary mucociliary clearance in the peripheral region of the lungs four weeks after saline spring treatment was found. The possibility of applying the saccharin sky-blue test for evaluating the success of saline spring treatment was examined. (author)

The rat is the most commonly used experimental animal and frequently being used to examine the pathophysiology in renal disease. Thus, it is important to apply techniques where renal function is assessed accurately. A special challenge exists in chronic unilateral renal disease for accurate measurement of single kidney GFR (SKGFR). We therefore examined the possibility of developing a method where SK GFR is measured in rats from the plasma clearance of 99mTc-DTPA and the reno graphically determined renal split function. A detailed comparison of renal clearance (Clr) and plasma clearance (Clp) of 99mTc-DTPA with that of 51-Cr-EDTA and 3H-inulin was performed in conscious rats with permanent catheters in the carotic artery, jugular vein and the urinary bladder using the following protocols: 1) Comparison of Clr of 99mTc-DTPA with 3H-inulin using a constant infusion clearance technique with four periods (P1-P4)(n=11), 2) comparison of Clr of 99m Tc-DTPA with that of 51Cr-EDTA or 3H-inulin (n=8) 3) comparison of Clr of 51Cr-EDTA and 3H-inulin using a constant infusion clearance technique with Clp of 99mTc-DTPA using a single injection technique with plasma sampling 4 hours after injection (n=11) and 4) comparison of Clp of 51Cr-EDTA with 99mTc-DTPA using the single injection technique (n=5). The results surprisingly showed that Clr of 99mTc-DTPA consistently was significantly lower than Clr of 51Cr-EDTA (548±146 vs. 860±49 □1/min/100g (avg±std);p<0.01) and of 3H-inulin (548±146 vs. 975±135 □1/min/100g; p<0.01: Interestingly, Clr of 99mTc-DTPA was progressively reduced with time in contrast to a constant Clr of inulin (P1:693±108 vs 939±118; P2:591±94 vs 877±17, P3:594±74 vs 947±131; P4:569±78 vs 991±122). Furthermore, Clp of 99mTc-DTPA was significantly lower than Clp of 51Cr-EDTA (874±130 vs. 1092±43 □1/min/100g;pclearance ratio DTPA/EDTA using constant infusion was 0.65±0.15 and 0.80±0.15 after single injection. In

This study evaluated the utility of the clearance time of inhaled diethylenetriamine pentaacetate (DTPA) to distinguish pulmonary vascular disease from early fibrosing alveolitis (FA) in patients with systemic sclerosis (SSc) It was hypothesized that this would be preserved in patients with vascular disease compared with FA, despite similar gas-transfer deficits and matching lung volumes, because of the preservation of alveolar epithelial integrity. All patients had SSc and were categorized into a control group (C; n=9), pulmonary vascular group (VAS; n=14) or FA group (n=14) dependent on the appearance on a computed tomography (CT) scan and the transfer factor of the lung for carbon monoxide (TL,CO) (VAS and FA {<=}70%, C {>=}80%). All patients had a forced vital capacity (FVC) of >80%. The TL,CO (median) was similar in the VAS (57.5%) and FA (60%) groups. There was a significant difference in median DTPA clearance half-times between FA (21.25 min) and VAS (46.5 min) (p=0.014) and between FA and C (84.5 min) (p=0.0004). No difference was found between VAS and C (p=0.0778). Follow-up data from the VAS group showed no subsequent development of FA on the CT scan and no decrease in FVC (n=13, mean 42 months). These results suggest that clearance of diethylenetriamine pentaacetate is preserved in patients likely to have pulmonary vascular disease and may be useful in distinguishing fibrosing alveolitis from vascular disease in systemic sclerosis. (au) 22 refs.

This study evaluated the utility of the clearance time of inhaled diethylenetriamine pentaacetate (DTPA) to distinguish pulmonary vascular disease from early fibrosing alveolitis (FA) in patients with systemic sclerosis (SSc) It was hypothesized that this would be preserved in patients with vascular disease compared with FA, despite similar gas-transfer deficits and matching lung volumes, because of the preservation of alveolar epithelial integrity. All patients had SSc and were categorized into a control group (C; n=9), pulmonary vascular group (VAS; n=14) or FA group (n=14) dependent on the appearance on a computed tomography (CT) scan and the transfer factor of the lung for carbon monoxide (TL,CO) (VAS and FA ≤70%, C ≥80%). All patients had a forced vital capacity (FVC) of >80%. The TL,CO (median) was similar in the VAS (57.5%) and FA (60%) groups. There was a significant difference in median DTPA clearance half-times between FA (21.25 min) and VAS (46.5 min) (p=0.014) and between FA and C (84.5 min) (p=0.0004). No difference was found between VAS and C (p=0.0778). Follow-up data from the VAS group showed no subsequent development of FA on the CT scan and no decrease in FVC (n=13, mean 42 months). These results suggest that clearance of diethylenetriamine pentaacetate is preserved in patients likely to have pulmonary vascular disease and may be useful in distinguishing fibrosing alveolitis from vascular disease in systemic sclerosis. (au)

With a view to improving the correlation of liver scintigraphy using 99mTc-DTPA-galactosyl human serum albumin (GSA) with hepatic function as indicated by indices such as LHL15, HH15, and laboratory data, the present study was carried out to set up a calibration curve (CC) for visual analysis. The application of 7 patterns of CC with different settings to a 1-min image (5 to 6 minutes after radiotracer injection) in 98 cases led to the preparation of 686 images whose correlation with hepatic function was examined by 15 observers via the grade classification of a five-point scoring system using visual analysis. The grade classification was as follows: grade 1 (faint cardiac blood-pool image), grade 2 (slight cardiac blood-pool image compared with liver uptake), grade 3 (almost the same appearance of cardiac blood-pool image and that of liver uptake), grade 4 (intense cardiac blood-pool image associated with possible liver uptake), and grade 5 (very slight liver uptake). The five-point scoring system could be used for CC slopes of 4.21, 4.79 and 2.79 (the above correlation was strongest for 4.21). The significance of inter-grade group differences in ICG-R15, LHL15 and heart/liver ratio was examined according to slope. With the CC slope of 4.21, a significant inter-grade group difference was observed between grades 1 and 2, grades 2 and 3, grades 3 and 4, and grades 4 and 5. In conclusion, when the value of the CC slope was 4.2, it was considered appropriate for grade classification on a five-point scoring system using visual analysis. (author)

Both fundamental and clinical studies were performed to improve the precision with which split renal clearance is calculated from the relation between renal clearance and the total renal uptake rate by using 99mTc-MAG3, which is mainly excreted into the proximal renal tubules. In the fundamental study, the most suitable kidney phantom threshold values for the extracted renal outline were investigated with regard to size, radioactivity, depth of the kidney phantom, and radioactivity in the background. In the clinical study, suitable timing to obtain additional images for making the ROI and the standard point for calculation of renal uptake rate were investigated. The results indicated that, although suitable threshold values were distributed from 25% to 45%, differences in size, solution activity, and the position of the phantom or BG activity did not have significant effects. Comparing 1-3 min with 2-5 min as the time for additional images for ROI, we found that renal areas using the former time showed higher values, and the correlation coefficient of the regression formula improved significantly. Comparison of the timing for the start of data acquisition with the end of the arterial phase as a standard point of calculating renal uptake rate showed improvement in the latter. (author)

In order to evaluate the role of the clearance of 99m Technetium chelated to diethylenetriamine-penta-acetate (99m Tc-DTPA) in amiodarone induced pulmonary disease, 40 individuals were studied in four groups. After spirometry, where a volume-time curve was registered, all individuals inhaled 740 MBq of 99m Tc-DTPA diluted in 4 ml of saline, for five minutes. Pulmonary images were obtained in a computerized scintillation camera and 9 regions of interest were selected. (author)

Measurement of 99mTc-MAG3 plasma clearance (CLmag) based on one-compartment model (MPC method) was applied to renal transplantation and evaluated for the factors which might affect the calculated results, especially concerning renal depth. Correlation coefficient of CLmag between MPC method using real renal depth and Russell or Bubeck single sampling method was good (r=0.852 or 0.876, respectively). Regression equation between MPC method and Russell method was y=1.044x-3.0 and was more closer to y=x than that between MPC method and Bubeck method. CLmag of MPC method calculated by estimated renal depth from the abdominal thickness was also similar to that by real renal depth. Even if the fixed renal depth, 4 cm, was applied, the coefficient and regression equation between MPC method and Russell method were r=0.884 and y=1.004x-10.2. In conclusion, MPC method is applicable to the evaluation of renal transplants. Though measuring renal depth is best, calculation with fixed renal depth of 4 cm might be practically acceptable. (author)

Background.The plasma sample method following a single injection of radioactive markers has been proved to be simple and accurate for the determination of glomerular filtration rate (GFR) in clinical practice. The aim of this study was to assess clinical accuracy of single-, two-and multi-sample methods. Patients and Methods. The study was performed on 50 patients with various degrees of renal dysfunction (29 males and 21 females; aged 27-90 years). As a reference the true GFR was determined by means of the two compartment model curve fitting 10 plasma following a single-injection of Tc99m-DTPA. The GFR was estimated by the three methods of single-, two and multi-sample between 75 and 300 min after the injection. The GFR by two and multi-sample methods was determined with the slope and intercept algorithm and its overestimation was corrected by Brochner-Mortensen's formula. Results. In all patients with a GFR between 12 and 169 ml/min/1.73m2, accuracy for the determination of GFR was identical in both the single-and five-sample methods. In 46 patients with a GFR higher than 30 ml/min/1.73m2, the single-sample method exhibited the lowest standard error of mean of difference in GFR. In 38 patients with a GFR lower than 120 ml/min/1.732, the two and five sample methods were more accurate than the single-sample one. The best combination of sampling time for the two samples was 120 min and 240 min after the injection. Conclusion. Accuracy of each plasma sample method depends on the preserved GFR. As a matter of practice, the single-sample method is the first choice for a patient who is expected to have a GFR higher than 30 ml/min/1.73m2. The two-sample method is indicated only in a patient with severe renal failure with a GFE lower than 30 ml/min/1.73m2 (au)

99mTc-MAG3 (mercaptoacetyltriglycine) has been proposed as a replacement for both 131I-hippuran and 99mTc-DTPA on clinical grounds. We undertook a prospective preliminary study to ascertain whether 99mTc-MAG3 works better than 99mTc-DTPA in the follow up of renal transplant recipients. Seventeen patients (21 renograms each MAG3 and DTPA) were studied, together, with a reference group of 10 patients in whom MAG3 and Hippuran clearance rates were determined simultaneously. As expected, 99mTc-MAG3 analog images were excellent and 99mTcMAG3 clearance correlated very well with 131I-hippuran clearance (r=0.978). MAG3 values were 60% of hippuran values. However, when the corresponding renographic and perfusion findings were faced with different diagnostic challenges, such as post transplant renal failure and rejection, 99mTc MAG3 did not differ from 99mTc-DTPA in a significant way. 99mTc-DTPA was superior to 99mTc-MAG3 in one case of rejection. (orig.)

The capacity of separated kidney function, estimated by means of {sup 131}I- or {sup 123}I-hippurate clearance, was compared with the capacity results from {sup 99m}TC-DMSA scintigraphy. There was found a good correlation (0.98) of the two methods. In patients with urine congestion the frequent high capacity in hippurate clearance in comparison to DMSA-scintigraphy on the affected kidney was evident. This results needs further investigations. In cases where it is necessary to evaluate the relative separated capacity of both sides, the hippurate clearance can be substituted by combination of DMSA-scintigraphy and isotope renogram. Considering surgical consequences, it is important to carry out both methods. (orig.).

A clinical study with 99mTc-DTPA-galactosyl serum albumin (99mTc-GSA) was performed in 10 patients with hepatobiliary disease. In this study, scintigraphic data and images with 99mTc-GSA were compared with several serological liver function tests, the hepatic blood perfusion index and image quality using 99mTc-DTPA-human serum albumin (99mTc-HSA). Dynamic and serial hepatic images were obtained over a 20 min period after 99mTc-GSA injection, and time activity curves from the heart and liver were generated. The blood clearance index (HH15), and the hepatic uptake index (LHL15) were calculated from each curve of the heart and liver, respectively. In addition, using two compartment fitting, the blood clearance (KH1, KH2) index was calculated, and using exponential fitting, the hepatic uptake index (KL) was calculated. The mean HH15 in liver cirrhosis (LC) group and non-LC group was 0.81±0.05, 0.64±0.10, respectively. The mean LHL15 in LC group and non-LC group was 0.79±0.04, 0.91±0.06, respectively. There were significant differences between non-LC group and LC group in HH15, and LHL15, KH1, and KL. There were also significant correlations of KH1 with HH15, and KL with LHL15. Parameters of 99mTc-GSA showed significant correlations with various liver functions. 99mTc-GSA scintigraphy showed clearer liver images in hepatobiliary disease than 99mTc-HSA. These results suggest that 99mTc-GSA scintigraphy is useful in estimating preserved liver function and hepatic morphology. (author)

Evaluation of glomerular function is a useful part of the diagnostic approach in animals suspected of having renal disease. Time-interval and background region of interest (bg ROI) selection are determining factors when calculating the glomerular filtration ratio (GFR) based on percentage uptake of (99m)technetium-labelled diethylene triamine penta-acetic acid ((99m)Tc-DTPA). Therefore, three different time intervals (60-120 s, 120-180 s, 60-180 s) and three different bg ROIs (C-shape, caudolateral, cranial + caudal) were investigated. In addition, global GFRs based on percentage dose uptake of (99m)Tc-DTPA for the different time-intervals and bg ROIs were compared with the global GFR based on (51)chromium-ethylene diaminic tetra-acetic acid ((51)Cr-EDTA) plasma clearance in nine healthy European domestic shorthair cats. Paired Student's t-tests and linear regression analysis were used to analyse the data. Different time intervals seemed to cause significant variation (P <0.01) in absolute GFR values, regardless of the choice of bg ROI. Significant differences (P <0.01) between bg ROIs were only observed in the 120-180s time interval between the C-shape and cranial + caudal bg ROI, and between the caudolateral and cranial + caudal bg ROI. The caudolateral bg ROI in the 60-180 s time interval showed the highest correlation coefficient (r = 0.882) between (99m)Tc-DTPA and (51)Cr-EDTA, although a significant difference (P <0.05) was present between both techniques. PMID:23349527

Chronic inhalant use is associated with significant toxic effects, including neurological, renal, hepatic, and pulmonary damage. However, there is a paucity of reports regarding respiratory complications in inhalant abusers. The aim of this study was to evaluate pulmonary epithelial permeability in the volatile substance abuse (VSA) using technetium-99m-labeled diethylenetriamine pentaacetic acid (Tc-99m DTPA) aerosol scintigraphy. This study included 18 patients with volatile substance abuse and 18 volunteer controls. All of patients and controls were smokers. Tc-99m DTPA aerosol scintigraphy was performed in all cases. Time-activity curves from each lung were generated and clearance half-time (T1/2) of Tc-99m DTPA were calculated. T1/2 of whole lung was calculated as a mean of the T1/2 of left and right lung. The T1/2 values of Tc-99m DTPA clearance in the substance abusers were significantly decreased as compared to the control group with respective mean values of 28.86±8.44, and 62.14±26.12 min (p=0.001). It was seen Tc-99m DTPA clearance from lung was faster as the duration of substance abuse was increased. Tc-99m DTPA pulmonary clearance is markedly accelerated in the volatile substance abuse. This suggests that inhalant abuse of substance may produce abnormalities in pulmonary alveolo-capillary membrane function. (author)

In quantitative renal function studies using Tc-99m DTPA and Tc-99m DMSA, the kidney depth is an important factor to control the gamma rays' absorption by the soft tissue. However, to date, this renal depth has been estimated from the patient's height and weight according to the formula of Toennesen. In the present study, we measured the kidney depth by ultrasonography and so determined the renal uptake of Tc-99m DTPA and Tc-99m DMSA. Using the kidney depth as measured by ultrasonography, the correlation coefficient between renal uptake of Tc-99m DTPA and GFR (determined by the clearance method) was 0.878 and that between renal uptake of Tc-99m DMSA and ERPF (determined from paraaminohippuran clearance) was 0.945. On the other hand, using the kidney depth as calculated by Toenneren's formula, the correlation coefficient between Tc-99m DTPA uptake and GFR was 0.849 and that between Tc-99m DMSA uptake and ERPF was 0.891. Thus, the renal depth measured by ultrasonography provided a closer correlation than that calculated according to Toenesen's formula. (author)

It is reported about inhalation scintiscanning with radioaerosols under the application of a gamma camera and a magnetic core- and tape memory, providing an interactive display. 89 patients suffering form various pulmonary diseases and 10 test persons with healthy lungs were investigated. The scintigraphic photos were not only evaluated visually, but also according to quantitative parameters, i.e. left/right distribution, degree of central deposition and mucociliary clearance. The latter resulted to be the most informative quantitative diagnostic method. In the 10 test persons with healthy lungs the scintigraphic images always showed a homogeneous distribution of radioactivity and a mucociliary half-time of 9.7 or 11.9 hours respectively was found. A central bronchial carcinoma provoked on the affected side of the lungs a reduced deposition of radioactivity, an increased central deposition and an accelerated mucociliary clearance. In patients suffering from peripheral bronchial carcinoma, pneumonia, pleural processes, pulmonary infarction, pulmonary circular focus or pneumothorax, only inconstant areas of reduced radioactivity deposition could be detected. However, these areas differed by shape, intensity and location from the central bronchial carcinoma. In 3 patients with pulmonary embolism, no pathologic changes could be detected only then, when no infarction occurred. In this case, also the quantitative parameters were normal. With chronical obstructive pulmonary diseases, diseases of the pulmonary framework and in cases of bronchial asthma a clearly pathologic image of the distribution of radioactivity resulted in all cases; in these a differentiation could only be achieved by additionally considering the quantitative parameters. (orig./MG)

The [99mTc-DTPA]2- and [99mTc-EDTA]1- were evaluated as radiotracers for short time hydrological studies. Their complex stability after labelling with 9.25 GBq of 99mTc, the behaviour against pH variations, from 5 to 9, in simulated solutions and in natural river waters and the sorption of these compounds on the river sediments, were tested in laboratory experiments. Finally field double tracing experiments were carried out for each of labelling complexes and Rhodamine WT. From recovery calculations not losses of the 99mTc activity were observed. The shape of the RTD curves of the [99mTc-DTPA]2- and [99mTc-EDTA]1were quite similar to the Rhodamine Wt ones. May be concluded that both complexes behaved conservatively on the studied environmental conditions. (author)

Aim: The main aim of this study was to evaluate the role of Tc-99m pertechnetate imaging in the management of hydatid cysts. Material and Methods: A total number of 10 patients with hydatid disease of the lungs were studied. Six had unilateral and four bilateral lung involvement. There were six males and four females (mean age= 31 years). In six patients serial planar images of the chest were obtained following intravenous injection of 2 mCi of Tc-99m pertechnetate using standard gamma camera computer systems. In few patients radioactivity was also introduced directly into the bronchus to detect the communicating channels (if any) between the cysts and respiratory system. Results: In all six patients active uptake of Tc-99m pertechnetate was seen immediately after intravenous injection of the radioactivity, and reaching a plateau by 3-5 minutes. On the other hand the time activity curve on the lungs showed a clear downward trend (clearancecurve) from the very beginning. The legion (cyst) to background (lungs) count ratios in all cases were found to be consistently high, ranging from 3:1 to 5:1. In two patients additional lung cysts (undetected by CT or x-rays) were detected. In three patients in addition to the active cysts, several low activity lesions were also detected. These corresponded to dead, inactive or complicated (infected) hydatid cysts. In few patients where radioactivity was introduced directly into the respiratory tracts, communication between the cyst and the main bronchus was demonstrated in one. In one such patient, where the radioactivity was introduced into the respiratory tract, a few minutes later discrete focal lesions were seen in the liver suggestive of multiple active hydatid cysts in the liver (concentrating Tc-99m pertechnetate which has been absorbed from the tracheo-bronchial tree into the vascular compartment). Conclusion: Tc-99m pertechnetate is actively taken up by the hydatid cysts. The differential uptake of radioactivity in the

Liver scintigraphy was performed using a newly developed radiopharmaceutical, Tc-99m-DTPA-galactosyl-human-serum-albumin (Tc-99m-GSA), which binds specifically to the receptors on the hepatic cell surface, in 15 patients with chronic liver disease. The scintigraphy was evaluated qualitatively and quantitatively, and the results were compared with those obtained from the Tc-99m-PMT or Tc-99m-sn-phytate scintigraphy, and the liver function tests. The Tc-99m-GSA scintigraphy showed clear liver images in chronic hepatitis. However, in liver cirrhosis, the liver images were not clear and the cardiac images still existed 40 minutes after administration of Tc-99m-GSA, suggesting that the image quality of the Tc-99m-GSA scintigrams may be inferior to that of Tc-99m-sn-phytate or Tc-99m-PMT in some cases of severe liver dysfunction. The time-activity curves of the heart and liver were analyzed by non-linear regression analysis. The clearance rate from plasma (Kd) were obtained from the time-activity curve of the heart, and the hepatic uptake rate (Ku), hepatic excretion rate (Ke) and peak time of hepatic uptake-excretion curve (PT) were obtained from the time-activity curve of the liver. Kd, Ku, and PT values were more significantly decreased or prolonged in the patients with chronic hepatitis. Kd, Ku, and PT values had positive correlations with the result of the serum liver function tests, ICG-R15 and ICG-K. Ku and PT values had also correlations with the histological degree of hepatic fibrosis. On the other hand, the indices obtained using Tc-99m-PMT or Tc-99m-sn-phytate did not have correlations with the histological degrees of hepatic fibrosis. It is concluded that the liver scintigraphy using Tc-99m-GSA may be useful and give different information from those with conventional liver scintigraphies in evaluating chronic liver diseases. (author)

This work is concerned on establishing the necessary comparative quality control biological parameters for the evaluation of locally produced renal pharmaceutical preparations viz. tin complexes of 99mTc-DTPA, 99mTc-GH, and 99mTc-DMSA using gel chromatography column scanning techniques. Radiochemical purity, labeling yields, organ distribution, blood clearance and plasma protein binding were used as a selected indicator for quality control. The higher renal accumulation and tissue distribution were apparent with 99mTc-DTPA in mice, while blood retention was considerably low. The blood clearance of 99mTc-DMSA was relatively slow, while that of 99mTc-GH was rapid. The binding of 99mTc- DTPA, 99mTc-GH and 99mTc-DMSA with plasma protein were found to be 5, 65, and 95 % at 1.0 h, respectively. The stability of these cold kits was not affected on storing at 37 deg C for 30 days. (author)

Citric acid was labeled with 99mTc with an efficiency of > 99%. The biodistribution of 99mTc-citrate was studied in mice with turpentine-induced abscesses in comparison to 67Ga-citrate. The max. abscess/muscle concentration ratios were 4.61 ± 1.92 (3 h) for 99mTc-citrate and 4.76 ± 2.04 (4 h) for 67Ga-citrate. Arthritis was induced in 10 rabbits by intra-articular injection of ovalbumin Scintigrams obtained 4 days later and at 3 h post-injection of 99mTc-citrate showed increased activity involving the synovium. The max. arthritic/contralateral knee ratio was 3.19 ± 1.29 (3 h) and 6.47 ± 3.71 (24 h) for 99mTc- and 67Ga-citrate, respectively. The blood clearancecurve of 99mTc-citrate in rabbits was biexponential with a fast and a slow component, compared to mono-exponential clearance of 67Ga-citrate. In 10 patients with rheumatoid arthritis whole-body scintigrams and spot images of involved joints indicated localization of the tracer in inflamed tissues. The mean target-to-soft tissue ratios were 3.04 ± 0.81 and 4.95 ± 2.56 for 99mTc-citrate and 99mTc-MDP, respectively. Renal clearance of radioactivity was evident from the scintigrams. Our results demonstrated that 99mTc-citrate is effective as a radiopharmaceutical for the visualization of inflammatory lesions and may be preferred to 67Ga-citrate due to the ideal physical characteristics of the radionuclide, easy preparation, low cost, early accumulation and the preference for the renal route of excretion. (Author)

Rheumatoid arthritis (RA) is a systemic autoimmune disorder primarily involving the joints. Lung alterations in RA may be primary or secondary to pharmacological treatments and may involve the alveoli, interstitium, airways and/or pleura. Technetium-99m diethylenetriaminepentaacetic acid (Tc-99m DTPA) aerosol inhalation scintigraphy is a sensitive and noninvasive test commonly employed to assess pulmonary epithelial membrane permeability. The purpose of this study was to investigate the changes of pulmonary alveolar epithelial permeability in patients with RA, to determine the relationship between the clearance rate of Tc-99m DTPA and pulmonary function test (PFT) results, and to determine the relationship between the clearance rate of Tc-99m DTPA and clinical parameters of disease. Twenty-five patients with RA but without lung alterations were included in the study. The patients were 22 females, and 3 males; mean age 53.6±8.7 years. Technetium-99m DTPA aerosol inhalation scintigraphy was performed on the study and healthy control groups. Clearance half times (T1/2) were calculated by placing a mono-exponential fit on the curves. Penetration index (PI) was calculated on the first-minute image. There were no significant differences in the mean T1/2 or mean PI values between the RA patients and control subjects. No correlation was found between the mean T1/2 values of Tc-99m DTPA clearance and activity of RA, clinical values, or the spirometric measurements except FEV1/FVC and functional status in RA patients (p=0.02, p=0.01, respectively). However, a weak correlation was found between duration of disease and T1/2 values of Tc-99m DTPA clearance (p=0.006). PI values tended to correlate with FEF25-75, although, this was not statistically significant (p=0.057). This study shows that no changes occur in alveolar-capillary permeability in RA patients without lung alterations. (author)

99mTc-galactosyl human serum albumin [99mTc-GSA] is a new scintigraphic agent which binds specifically to asialoglycoprotein-receptor on the hepatic cell membrane. The new liver scintigraphy using 99mTc-GSA was performed in 30 patients with chronic liver disease to evaluate the residual liver function. Two parameters were obtained from 99mTc-GSA time activity curves of both the heart and the liver. One was [HH15] (clearance index), which was the ratio of radioactivity of the liver at 15 min over that at 3 min after injection. The other was [LHL15] (receptor index), the ratio of radioactivity of the liver over that of the liver plus heart at 15 min. Significant decrease in LHL15 and increase in HH15 value were observed in accordance with severities of the liver damage and clinical aggravation. These parameters correlated significantly with Child-Pugh score, glucagon test, ICG-R15, serum albumin levels, cholinesterase, prothrombin time and hepaplastin test also. In conclusion, these findings indicate that 99mTc-GSA liver scintigraphy is useful for evaluating the liver flunction in patients with chronic liver disease. (author)

Precise diagnosis of complication after renal transplantation is necessary for treatment decision making. Acute rejection is one of the most serious but treatable complications. It is well known that mean parenchymal transit time (MPTT) arises with decreased function of Kidneys. In this study we evaluated changes of MPTT and de convoluted curve to asses the diagnostic value of these parameters rejection. This investigation was carried out on 27 complicated transplanted kidneys (11 cases with acute rejection - A R- and 16 cases with other complication-O C-) and 13 normal grafts by Tc-99-DTPA scintigraphy. MPPT, the time of 20% (T 20) and %80 (T 80) of curve pla tue as well as the ratio of T 20/T 80 were calculated according to de convoluted curve. In normal grafts Matt was 2.03+0.54 which arise d in A R (4.05+0.2), P0.1) between Ar and O C, however, the ratio of T 20/T 80 was higher in A R compared to O C (2.41+0.23 versus 1.77+0.27, P<0.001). With consideration of 2.1 as T 20. T 80 threshold, sensitivity and accuracy values for diagnosis of A R were 90%, 87% and 89% respectively. MPTT is a sensitive parameter to diagnosis of complicated transplanted kidney, but with calculation of T 20/T 80, we can obtain an accurate parameter for diagnosis for of acute rejection

The blood flow of the dog urinary bladder measured by radioactive microsphere technique was compared to the clearance of locally injected 99mTechnetium pertechnate (99mTc) in the bladder wall. In semilogarithmic plots the 99mTc washout curves showed a multiexponential course. From the initial slo...

We evaluated 99mTc-labeled mercaptoacetyltriglycine (99mTc-MAG3)-biocytin as a hepatobiliary imaging agent in the absence and presence of bilirubin in mice. We then compared its pharmacokinetic parameters; peak liver/heart activity ratio (rmax) and half clearance time (HCT) with those of 99mTc-labeled diisopropyl-iminodiacetic acid (99mTc-disofenin). Balb/c mice were injected intravenously with hepatobiliary agent (99mTc-MAG3-biocytin or 99mTc-disofenin) alone or in combination with bilirubin at two doses (7 and 14 mg/kg) dissolved in 5% human serum albumin. Images were acquired every 15 s for 30 min with a gamma-camera equipped with a pinhole collimator. Dynamic images showed rapid hepatic uptake of 99mTc-MAG3-biocytin, with rapid clearance from the blood and rapid excretion via the biliary system. Its hepatic uptake was not affected by bilirubin coinjection, whereas 99mTc-disofenin coinjected with bilirubin showed a higher blood background than 99mTc-disofenin alone. These qualitative findings were reflected in pharmacokinetic parameters, rmax and HCT. The rmax was obtained from plots of time versus liver/heart activity ratios obtained in equal-area regions of interest over the heart and liver. The HCT was calculated from the hepatic clearancecurve from plots of time versus liver activity. 99mTc-MAG3-biocytin without bilirubin coinjection showed an rmax of 8.9±1.3 and an HCT of 399±36 s. These values did not change even when 14 mg/kg of bilirubin were coinjected. By contrast, the parameters for 99mTc-disofenin with bilirubin were significantly (pmax was decreased from 7.9±2.5 to 1.4±0.2 and HCT was increased from 292±32 s to 782±133 s. 99mTc-MAG3-biocytin hepatobiliary scintigraphy in mice is not affected by bilirubin coinjection, and this hepatobiliary agent appears to offer promise for estimating hepatic function in patients with high bilirubin levels

Effective hepatic blood flow (EHBF) was measured from an uptake constant using single blood sampling and 99mTc-PMT hepatobiliary SPECT data. After intravenous injection of 3 mCi (111MBq) of 99mTc-PMT, serial 1 min SPECT data were obtained for 7 minutes. A time activity curve (TAC) over the heart, that was normalized with the 5 minutes venous sample concentration (%/dose/m1), was used as a blood clearancecurve (B(t)). And a TAC of the whole liver, that was normalized with the injected dose of 99mTc-PMT (%/dose), was used as a hepatogram (L(t)). An uptake constant representing EHBF, was estimated from the Rutland's method L. (t)/B(t) was plotted against ∫otB(t)dt/B(t), and the slope of the least square fitted straight line was determined as the uptake constant. In 16 cases, significant correlation was obtained between the 99mTc-PMT hepatic uptake at 5 minutes and the EHBF estimated from the blood clearance (r=0.85,p99mTc-PMT SPECT data enables us to estimate EHBF with single venous sampling and in relatively short acquisition time. This method is thought to be very valuable in clinical practice. (author)

Technetium-99m ({sup 99m}Tc) tetrofosmin has been used as a tumor-seeking agent. However, its role in detecting lymphomas has not been widely investigated. The aim of the present study was to determine the uptake and clearance characteristics of {sup 99m}Tc tetrofosmin in lymphoma cell lines. {sup 99m}Tc sestamibi was also evaluated for comparison. Three lymphoma cell lines (U-937: monocyte-like, histiocytic lymphoma, human; RAMOS: B-lymphoma cell line, American Burkitt lymphoma, lymphoblastoid, human; Hs445: Hodgkin's disease, lymphoid, human) were studied. After incubation of radiotracers {sup 99m}Tc tetrofosmin and {sup 99m}Tc sestamibi in medium for 0, 10, 20, 30, 60, 120 and 180 min, the uptake and clearance of each radiotracer were measured in the three lymphoma cell lines. The uptake of {sup 99m}Tc tetrofosmin was lower than that of {sup 99m}Tc sestamibi in these lymphoma cell lines. Among the three cell lines, Hs445 showed the greatest {sup 99m}Tc tetrofosmin uptake capacity. RAMOS and U-937 showed similar {sup 99m}Tc tetrofosmin uptake capacities. {sup 99m}Tc tetrofosmin accumulated in the three tested lymphoma cell lines, especially in the Hodgkin's disease cell line. However, in comparison with {sup 99m}Tc sestamibi, {sup 99m}Tc tetrofosmin may not be the best radiotracer for detection of lymphoma.

Behcet's disease (BD) is a multisystem disorder characterized by vasculitis, and consists of a triad of recurrent ulcers of the oral and genital mucosa with relapsing uveitis. The prevalance of pulmonary involvement varies in the range of 1-10% in various studies and its complications are severe and life threatening. In this study, we investigated the changes of pulmonary epithelial permeability of patients with BD using technetium-99m diethylene triamine penta-acetic acid (99mTc-DTPA) aerosol scintigraphy, so as to begin the therapy regimen as soon as possible. Twenty-one nonsmoking patients with BD (8 women, 13 men; mean age 38.67±8.86 years) and 15 healthy volunteer nonsmoking controls (8 women, 7 men; mean age 50.87±12.45 years) underwent 99mTc-DTPA aerosol inhalation scintigraphy and pulmonary function tests (PFTs). Subjects inhaled 1480 MBq of 99mTc-DTPA for 4 min in the supine position. Scintigraphic data were recorded dynamically (1 frame/min) in the posterior projection on a 64 x 64 matrix for a 30-min period using a double-headed gamma camera (Infinia, GE, Tirat Hacarmel, Israel) equipped with a low-energy all-purpose parallel hole collimator. Half time of 99mTc-DTPA clearance (T1/2) was calculated by placing a mono-exponential fit on the curves. Penetration index (PI) was also calculated by dividing the peripheral total counts by the sum of the peripheral and central total counts on the first minute image, in order to quantify the distribution of the inhaled aerosol. The clearance half time of 99mTc-DTPA radioaerosols in the BD patients (24.81±6.22 min) was faster than in the normal control group (46.53±22.41 min) (P=0.004). There was also a significant difference between PI of the patients with BD (0.15±0.03) and that of the controls (0.21±0.06) (P=0.002). No correlation was found between the mean T1/2 values of 99mTc-DTPA clearance or the spirometric measurements in the BD patients. Penetration indices were not correlated with PET in the BD

A wide range of pharmaceuticals for labeling with Tc-99m, developed by the Soreq Radiopharmaceuticals Department, is described. Details of the production and quality control of 13 kits are given, as well as the range of results required for consistently high quality imaging agents

It is vital to accurately evaluate renal function in children with vesicoureteral reflux. To determine whether quantitative split renal function testing methods using 99mTc-DTPA and 99mTc-DMSA renoscintigraphy reflect renal function as accurately in children as in adults, 99mTc-DTPA and 99mTc-DMSA renoscintigraphies were performed in 21 children with vesicoureteral reflux within 5 days of each other for a total of 40 times. There were 12 boys and 9 girls ranging in age from 2 months to 16 years (mean, 6.8 years). The kidney depth was measured by ultrasonography. The correlation coefficient between 99mTcDTPA and 99mTc-DMSA total renal uptake was 0.275, and the correlation coefficients between 99mTc-DTPA and 99mTc-DMSA total renal uptakes and creatinine clearance were 0.402 and 0.522, respectively. The correlation coefficient between the accumulation count ratio (R/R+L) in 99mTc-DTPA and that in 99mTc-DMSA was 0.974. The total renal uptake obtained from 99mTc-DTPA and 99mTc-DMSA renoscintigraphy is not as reliable in children as in adults, and at present it is most appropriate to use a combination of accumulation count ratio (R/R+L) and 24 hr creatinine clearance value as examinations to evaluate general renal function. (author)

To assess the usefulness of own EC-99mTc complex for the kidney function examination, the renoscintigraphy with EC-99mTc and clearance determinations were performed. During renoscintigraphy the kidney images were of superb quality, with overlaying organs (liver, spleen) not visualized. Renograms showed typical shapes, their TMAX and T1/2 values being insignificantly different from the obtained with other radiopharmaceuticals, used in renoscintigraphy (MAG3, hippuran). Very strict correlations were found between values of EC-99mTc and OIH-131I clearances (r=0.91) and excretion rate constants (r=0.92) of both radiopharmaceuticals. The correlation enabled formulation of an equation by which ERPF could be established from EC-99mTc clearance: ERPFOIH=1.245 x ClEC+51.52. On the basis of this equation a lower boundary of the normal EC-99mTc clearance was established; it amounts to 300 ml/min/1.73 m2. (author). 17 refs, 5 figs, 1 tab

Background: We report on a case of preoperative scintigraphic and intraoperative scintimetric confirmation of an ectopic parathyroid adenoma with Tc-99m Tetrofosmin in a 52-year old patient with persistent hyperparathyroidism after unsuccessful primary preoperative localization and reoperation. Methods: In preoperative localization study, dynamic, sequential static scans and SPECT of the neck and mediastinum were performed using Tc-99m Sestamibi and Tc-99m Tetrofosmin. Reoperation was performed by help of a hand-held gamma-probe for intraoperative scintimetric localization after preoperative injection of Tc-99m Tetrofosmin. Results: An ectopic adenoma could be detected preoperatively with both tracers. Tc-99m Tetrofosmin showed no significant difference in image quality vs. Tc-99m Sestamibi. The adenoma could also be detected scintimetrically by elevated count-rates. Conclusions: This case gives promise for Tc-99m Tetrofosmin to be a possible alternative in parathyroid imaging with similar imaging properties and slight theoretical advantages concerning background clearance, radiation exposure and constitution over Tc-99m Sestamibi. Intraoperative localization and confirmation of ectopic parathyroid adenoma, eventually with a geometrically adapted gamma-probe, seems to be possible. Whether there are significant advantages resulting in a possible reduction of operating time, should be evaluated in further studies. (author)

Gel chromatography scanning technique (GCS) was used to study the radioanalytical behaviour of 99mTc-tin colloid and 99mTc-sulphur colloid kits. Sepharose has been found to be more accurate and versatile than the other conventional analytical procedures for radioanalytical evaluation of 99mTc-labelled colloids. The obtained radioanalytical results showed that 99mTc-sulphur colloid is more susceptible than the 99mTc-tin colloids to change due to the analytical environment. This is related to the nature of oxidation state of technetium atom in both colloids. The formation of 99mTc-tin colloid is achieved within few minutes after pertechnetate addition, while labeling of sulphur colloid is accomplished through a rather slow process. The organ distribution in mice shows that more than 90% of the injected dose of both colloids are accumulated in the liver, which proved the colloid labeling and optimal size particle. The minor size difference in the blood residual activity is due to the presence of hydrophilic stabilizer in 99mTc-sulphur colloid. The blood clearance study in rabbits showed that the biological half-times of activity disappearance of fast phase are longer periods extend to 125 and 65 minutes to 99mTc-tin and 99mTc-sulphur colloids, respectively. The in vitro plasma protein binding studies revealed by the GSC method showed that about 85% of 99mTc-tin colloid and 16% of 99mTc-sulphur colloid were bound to plasma protein, which proved that it does not influence the in vivo kinetics of both colloids

Quality control (QC) studies were done of three locally produced renal preparations of 99mTc- DTPA, 99mTc-GH and 99mTc-DMSA, as part of the production activity before the Gulf war. These studies were performed using gel chromatography column scanning (GCS) technique, although there are other alternative techniques. These kits were tested for radiochemical purity, and the labeling yields were found to be excellent. Biological studies included the following parameters: organ distribution (in mice, rats and rabbits), blood clearance in rabbits, and plasma protein binding in rats at different time intervals. Poor renal concentration of three agents in mice was significant at two time intervals. The tissue distribution in mice of DTPA, GH, and DMSA kits, which were stored at 37 deg. C for 30 days, after intravenous injection of the radioactivity at 5, 30, and 60 minutes, respectively, is presented. Blood retention of the renal agents was considerably low compared to those in rats and rabbits at the respective time intervals. The blood clearance of 99mTc-DMSA was relatively slow, and 99mTc-GH has rapid blood clearance, identical with that of 99mTc-DTPA for the first 20 minutes but slower thereafter. The binding of DTPA, GH and DMSA with plasma protein was 5, 65, 95 % at 1 h, respectively. Various amounts of tin (II) (as SnCl2), were used in the kits, with up to 10 times more of the usual dose for respective tin-complex. It was observed that there was no significant variation of the organ distribution in mice

The aim of this study was to label ubiquicidin fragment 29-41 (UBI) and biotin with 99mTc and evaluate their feasibility as infection imaging agents for in vivo use. 99mTc-UBI, labelled by a direct method, showed high in vitro and in vivo stability, specific uptake at the site of infection, rapid background clearance, minimal accumulation in non-target tissues and rapid detection of infection sites. 99mTc labelled biotin showed in vitro and in vivo stability, fast renal clearance and ability to detect infection and sterile inflammation processes in mice. Because of their stability and biological properties, both agents could be used in clinical applications. (author)

We have previously reported that the hepatic uptake of Tc-99m-mercaptoacetyltriglycine (MAG3)-biocytin was not affected by coinjecting bilirubin in mice whereas the uptake of Tc-99m-diisopropyliminodiacetic acid (DISIDA) was inhibited (Kim et al. J Nucl Med, 38 : 50 p, 1997). The aim of this study was to investigate whether the hepatic uptake of Tc-99m-MAG3-biocytin or Tc-99m-DISIDA could be inhibited by biotin and biocytin. The Balb/c mice (female, 20g, n=5-8) were injected i.v. with the hepatobiliary agents alone (15-22 MBq/20-40 {mu}g) or together with inhibitors at two doses (14 and 28 mg/kg). For pharmacokinetic studies, images were acquired at 10-sec intervals for 20 min using a gamma camera equipped with a pin-hole collimator (d= 1 mm), starting immediately after intravenous injection. Pharmacokinetic parameters, peak liver/heart ratio (Rmax) and hepatic half clearance time (HCT), were calculated from liver and heart time-acitivity curves from regions-of-interest. Dynamic images showed rapid hepatic uptake inhibition was characterized by persistent high blood background. These qualitative scintigraphic findings were reflected in the pharmacokinetic parameters. Tc-99m-MAG3-biocytin without inhibitor coinjection showed Rmax of 9.3 and HCT of 383 sec. These parameters did not change significantly when bilirubin or biotin was coinjected, but did change significantly (P<0.05) for biocytin only at the higher dose: 52% decrease in HCT. In contrast, the parameters for Tc-99m-DISIDA (Rmax of 9.2 and HCT of 258 sec) were greatly affected (P<0.01) by biotin (79% decrease in Rman and 2-fold increase in HCT) even at 14 mg/kg concentration. We concluded that Tc-99m-MAG3-biocytin is less sensitive to inhibition by bilirubin, biotin, and biocytin than Tc-99m-DISIDA. Tc-99m-MAG3-biocytin appears to be a promising hepatobiliary imaging agent for hepatic function studies and may also be a useful tool to investigate the hepatic uptake mechanism of biotin derivatives in vivo.

We have previously reported that the hepatic uptake of Tc-99m-mercaptoacetyltriglycine (MAG3)-biocytin was not affected by coinjecting bilirubin in mice whereas the uptake of Tc-99m-diisopropyliminodiacetic acid (DISIDA) was inhibited (Kim et al. J Nucl Med, 38 : 50 p, 1997). The aim of this study was to investigate whether the hepatic uptake of Tc-99m-MAG3-biocytin or Tc-99m-DISIDA could be inhibited by biotin and biocytin. The Balb/c mice (female, 20g, n=5-8) were injected i.v. with the hepatobiliary agents alone (15-22 MBq/20-40 μg) or together with inhibitors at two doses (14 and 28 mg/kg). For pharmacokinetic studies, images were acquired at 10-sec intervals for 20 min using a gamma camera equipped with a pin-hole collimator (d= 1 mm), starting immediately after intravenous injection. Pharmacokinetic parameters, peak liver/heart ratio (Rmax) and hepatic half clearance time (HCT), were calculated from liver and heart time-acitivity curves from regions-of-interest. Dynamic images showed rapid hepatic uptake inhibition was characterized by persistent high blood background. These qualitative scintigraphic findings were reflected in the pharmacokinetic parameters. Tc-99m-MAG3-biocytin without inhibitor coinjection showed Rmax of 9.3 and HCT of 383 sec. These parameters did not change significantly when bilirubin or biotin was coinjected, but did change significantly (P<0.05) for biocytin only at the higher dose: 52% decrease in HCT. In contrast, the parameters for Tc-99m-DISIDA (Rmax of 9.2 and HCT of 258 sec) were greatly affected (P<0.01) by biotin (79% decrease in Rman and 2-fold increase in HCT) even at 14 mg/kg concentration. We concluded that Tc-99m-MAG3-biocytin is less sensitive to inhibition by bilirubin, biotin, and biocytin than Tc-99m-DISIDA. Tc-99m-MAG3-biocytin appears to be a promising hepatobiliary imaging agent for hepatic function studies and may also be a useful tool to investigate the hepatic uptake mechanism of biotin derivatives in vivo

Psycho pharmacology has been discovering much about the D 2 dopamine receptors and their interrelationship to brain pathologies such as Parkinson's Disease, Schizophrenia and Huntington Disease. Those biological receptors have got affinity with dopamine endogenous agent, so that they complex and, in non pathological individuals, the biological receptors contribute to bring the levels of dopamine and free acetylcholine into equilibrium. The Spiperon Dithiocarbamate (SPDC) from Spiperon is synthesized and its complexation with Technetium-99m has been prepared with its reaction parameters after being studied and improved. The SPDC- 99m Tc complex biological distribution has been made in Wistar rats and the uptake of spleen, heart, liver, stomach, lung, kidney, blood, intestine and brain have been resolved. The plasmatic clearancecurve has been based on Wistar rats data and the Know-how of the kit ( for label SPDC with 99m Tc) has been achieved. (author)

The radiolabeling of the liposome surface can be a useful tool for in vivo tracking of therapeutic drug loaded liposomes. We investigated radiolabeling therapeutic drug (i.e. an antibiotic, amikacin) loaded liposomes with (99m)Tc, nebulization properties of (99m)Tc-labeled liposomal amikacin for inhalation ((99m)Tc-LAI), and its stability by size exclusion low-pressure liquid chromatography (LPLC). LAI was reacted with (99m)Tc using SnCl2 dissolved in ascorbic acid as a reducing agent for 10 min at room temperature. The labeled products were then purified by anion exchange resin. The purified (99m)Tc-LAI in 1.5% NaCl solution was incubated at 4 °C to assess its stability by LPLC. The purified (99m)Tc-LAI was subjected to studies with a clinically used nebulizer (PARI eFlow®) and the Anderson Cascade Impactor (ACI). The use of ascorbic acid at 0.91 mM resulted in a quantitative labeling efficiency. The LPLC profile showed that the liposomal peak of LAI detected by a UV monitor at both 200 nm and 254 nm overlapped with the radioactivity peak of (99m)Tc-LAI, indicating that (99m)Tc-LAI is suitable for tracing LAI. The ACI study demonstrated that the aerosol droplet size distribution determined gravimetrically was similar to that determined by radioactivity. The liposome surface labeling method using SnCl₂ in 0.91 mM ascorbic acid produced (99m)Tc-LAI with a high labeling efficiency and stability that are adequate to evaluate the deposition and clearance of inhaled LAI in the lung by gamma scintigraphy. PMID:23879241

Technetium-99m-labeled alendronate is a new radiopharmaceutical for bone scanning developed under strict quality control at the INNSZ. The purpose of this work was to compare the radiopharmacokinetic data and the dosimetry of 99mTc-ABP and 99mTc-MDP in 10 volunteers, after it was tested in laboratory animals. 99mTc-ABP has shorter mean residence time (MRT) and t(1(2)) β; is less protein bound; has a higher renal clearance; smaller Vdss, and similar bone uptake at 1 and 2 h. 99mTc-ABP gives less radiation exposure to the patient with a 740 MBq dose, and the quality of the bone scan is excellent. 99mTc-ABP is a better radiopharmaceutical than 99mTc-MDP for bone scanning

Our previous studies showed that the efflux rate of technetium-99m methoxyisobutylisonitrile (MIBI) is directly correlated to P-glycoprotein (Pgp) levels in breast carcinoma. The aim of this study was to test whether the Pgp-dependent efflux of 99mTc-MIBI is related to the apoptotic pathway activation in breast carcinoma. Thirty-three untreated non-consecutive patients were intravenously injected with 740 MBq 99mTc-MIBI and serial images were obtained up to 4 h. The rate of efflux was determined by mono-exponential fitting of decay-corrected time-activity curves. Tumour specimens were then obtained at surgery and processed for the determination of the apoptotic index by in situ end-labelling of DNA fragments (Tunel). The rate of tumour cell proliferation was also determined using Ki67 monoclonal antibody. All breast carcinomas showed focal uptake of 99mTc-MIBI and the time to half clearance varied between 85 and 574 min. The apoptotic index ranged between 0.3% and 4.2%, whereas the rate of proliferation varied between 13% and 40%. We found a positive and significant correlation between the apoptotic index and the rate of proliferation (r=0.79, P99mTc-MIBI was directly and significantly correlated with the apoptotic index (r=0.74, P99mTc-MIBI (r=0.57, P99mTc-MIBI sequestration, a model for the dynamic coupling of Pgp-dependent 99mTc-MIBI efflux and apoptotic pathway activation may be derived. (orig.)

A formulation of stannous-diethyl-IDA freeze-dried kit, containing 50 mg diethyl-IDA and 0.4 mg hydrated stannous chloride, to be labelled with technetium was developed for hepatobiliary scintigraphy. The organ distribution data of 99mTc-diethyl-IDA in mice for 60 min post injection were satisfactory. The radiopharmaceutical exhibits rapid blood clearance, great hepatic clearance and very short hepatocyte transit time. Uptake of the radiopharmaceutical was highest in mouse liver and intestine. The renal uptake of the HB agent in mice is relatively low. Blood clearance data showed that the HB agent is rapidly cleared. (author) 20 refs.; 4 tabs

Tc-99m labelled 2,6-diethylphenylcarbamoylmethyliminodiacetic acid (EHIDA) is a non-toxic radiopharmaceutical that was found to undergo rapid biliary excretion in a normal human, with accumulation of radioactivity in the gall bladder and intestine. Images in normal subjects and nonjaundiced patients showed rapid concentration of tracer by the liver and the passage of the same into the intestine within 15 to 40 minutes, with or without visualization of the gall bladder. In the jaundiced patient, the tracer blood clearance was delayed and urinary excretion was increased. Tc-99m EHIDA has been extensively investigated in 1634 patients to evaluate its performance in the diagnosis of hepatobiliary disorders

It has been shown that some radiopharmaceuticals can cross the placental barrier and enter into fetal circulation. The objective of this study was to investigate placental transfer of cardiac perfusion imaging radiopharmaceuticals (Tc-99m sestamibi, Tc-99m tetrofosmin and TI-201 thallous chloride (Tl+ -201)) in pregnant guinea pigs and in-vitro mechanism of the transfer using human placental lobule. Pregnant guinea pigs in the first, second and third trimesters were used. Following intravenous injection of Tc-99m sestamibi, Tc-99m tetrofosmin or Tl+ -201 the guinea pig was imaged using a gamma camera; killed and the fetuses removed. Each fetus was then imaged separately using a low energy general-purpose collimator. The placentas, ovary, and fetal hearts, lungs, liver, kidneys and blood were then removed and the radio-activity in each organ along with a 1.0 ml standard solution was counted separately in a dose calibrator. For the in-vitro experiment, the effect of ouabain on the transfer of Tl+ -201 and tritiated water (as internal reference marker) in the maternal-fetal direction was studied in human placentas (collected postpartum) from normal uncomplicated pregnancies and suitable lobules perfused with either normal or ouabain-treated perfusate. The differential transport rate of Tl+ -201 in the maternal-fetal direction was measured as time taken in minutes for 50% fraction of Tl+ -201 (TR50 ) to be transported across the fetal vein and expressed as the ratio of the TR50 of Tl+ -201 to tritiated water (TR50 index). The following pharmacokinetic parameters were also measured: the area under the curve, clearance and absorption rate indices. Neither Tc-99m sestamibi nor Tc-99m tetrofosmin was transferred across the placental barrier while 1.7 ± 0.5% of the injected activity (0.027 ± 0.005 % per gram) of Tl+ -201 radioactivity during the third trimester was transferred across the placenta into fetal circulation. Most of the radioactivity from Tl+ -201 in the fetus

The pulmonary clearance of aerosol DTPA-Tc99m is a technology easy to use, well support by patients with immediate results. With the pneumonia at Pneumocystis Carinii (PPC), the clearance is more sensitive and more specific than the thoracic scintigraphy with Ga67. Used with a thorax radiography, results will lead to three directions: High probability of PPC, di phasic curve and very fast T50, equal inferior to 5,10 mn. Low probability of PPC, monoexponential curve and abnormal thorax radiography or di phasic curve with a value T50 superior to 5,10 mn. With these patients other explorations will be made (Ga67, biopsy) and if possible search pulmonary tuberculosis. Extra pulmonary pathology: monoexponential curve associated with a normal thoracic radiography. 2 figs

Crohn's disease (CD) is a chronic inflammatory bowel disease that may involve the whole gut. Marked intestinal T cell and macrophage activation is a key feature of the disease. Polymorphonuclear cell infiltration is also observed in the diseased gut, mainly during active inflammation. Scintigraphic detection of granulocytes and activated lymphocytes infiltrating the gut wall may be useful in identifying a subgroup of patients with clinically inactive CD who are undergoing early clinical relapse. The aims of the present study were (a) to compare the effectiveness of scintigraphy with 99mTc-labelled interleukin-2 (99mTc-IL2) and with 99mTc-HMPAO labelled granulocytes (99mTc-WBC) in detecting the presence and extent of bowel inflammation in patients with long-term inactive CD (>12 months) and (b) to assess the accuracy of these techniques in predicting future disease relapse. We studied 29 patients with ileal and/or colonic CD in stable clinical remission (Crohn's Disease Activity Index 99mTc-IL2 and 99mTc-WBC scintigraphy in order to evaluate the extent of acute and chronic inflammation in the bowel. Planar and single-photon emission tomography images were acquired in each patient at 1 h p.i. For quantitative analysis of 99mTc-IL2 uptake, the abdomen was divided into 32 regions of interest. Despite the absence of symptoms, 18 patients (62%) showed a positive 99mTc-IL2 and 18 (62%) a positive 99mTc-WBC scan. Only 12 patients (41.4% of the total group) were positive on both scans, and the sites of IL2 and granulocyte bowel uptake were usually located in different segments, indicating that in CD, acute and chronic inflammation can be present in different sites. As far as the prognostic role of the two scans in predicting future disease relapse is concerned, both 99mTc-IL2 and 99mTc-WBC scintigraphy showed a high negative predictive value (1.00 and 0.91, respectively) but a weak positive predictive value (0.44 and 0.39, respectively). Nevertheless, Kaplan-Meier curves

It is vital to accurately evaluate renal function in children with vesicoureteral reflux. To determine whether quantitative split renal function testing methods using {sup 99m}Tc-DTPA and {sup 99m}Tc-DMSA renoscintigraphy reflect renal function as accurately in children as in adults, {sup 99m}Tc-DTPA and {sup 99m}Tc-DMSA renoscintigraphies were performed in 21 children with vesicoureteral reflux within 5 days of each other for a total of 40 times. There were 12 boys and 9 girls ranging in age from 2 months to 16 years (mean, 6.8 years). The kidney depth was measured by ultrasonography. The correlation coefficient between {sup 99m}TcDTPA and {sup 99m}Tc-DMSA total renal uptake was 0.275, and the correlation coefficients between {sup 99m}Tc-DTPA and {sup 99m}Tc-DMSA total renal uptakes and creatinine clearance were 0.402 and 0.522, respectively. The correlation coefficient between the accumulation count ratio (R/R+L) in {sup 99m}Tc-DTPA and that in {sup 99m}Tc-DMSA was 0.974. The total renal uptake obtained from {sup 99m}Tc-DTPA and {sup 99m}Tc-DMSA renoscintigraphy is not as reliable in children as in adults, and at present it is most appropriate to use a combination of accumulation count ratio (R/R+L) and 24 hr creatinine clearance value as examinations to evaluate general renal function. (author).

We compare glomerular filtration rate by DTPA Renogram (DTPA-GFR) with creatinine clearance (CC) and Glomerular filtration rate from Schwartz formula (Schwartz-GFR). The need for using (DTPA-GFR) method raised from the practical difficulties in getting an accurate (CC) in pediatric population. From Sep-2001 to May-2005, 48 patients aged 1month to 18 years, underwent (DTPA-GFR) and (Schwartz-GFR). 18 had also (CC). Comparison were made among these measurements also accounting for age groups. We found a better correlation between (DTPA-GFR) and (CC) Pearson = 0,895. (Schwartz)/(CC) comparison showed a slightly lower correlation Pearson = 0,857. The worst correlation was found comparing (DTPA-GFR)/(Schwartz-GFR) in children < 3 yr Pearson = 0,560. As we found a better correlation between (DTPA-GFR)/(CC) than (DTPA-GFR)/(Schwartz-GFR), DTPA-GFR could be considered reliable method in evaluating renal function in children having difficulties to get a Creatinine Clearance (au)

High diagnostic efficiency of sup(99m)Tc-phytic frostimag colloid for studies of the anatomic-topographic characteristics of the liver and spleen, and its advantages over sup(99m)Tc-sulphide colloid for studies of splenic clearance have been shown. The profile scanner (MNIRRi-GAMMA) was used for the quality control over the preparation of Tc-labelled colloids

The aim was to compare the relative renal functions measured with technetium-99m dimercaptosuccinic acid (99mTc-DMSA) and technetium-99m diethylenetriaminepentaacetic acid (99mTc-DTPA) in children with renal diseases. Relative renal function of 128 children who applied to three hospitals from 2009 to 2011 were analyzed retrospectively. The mean value measured with 99mTc-DTPA and 99mTc-DMSA were 51.58 ± 14.95 and 51.96 ± 14.99 for the right kidney, 47.87 ± 15.27 and 47.94 ± 15.17 for the left kidney, respectively. A significant positive correlation was found between the relative renal functions (r = 0.963, P renal function, 99mTc-DTPA can be another choice for the calculation of relative renal function without a complementary DMSA scan particularly in pediatric patients who require renogram curve and GFR calculations. PMID:25538484

Tetrapeptides are a class of N4-tetraligands that can efficiently bind 99mTc. In fact, tetrapeptides can be considered as derivatives of mercaptoacetyltriglycine (MAG3) in which the mercaptoacetyl moiety is replaced by a more stable and easier to handle aminoacyl group. Direct labelling of tetrapeptides with99m Tc in alkaline medium (pH ≥ 11) in the presence of stannous ions gave a high yield (>95%) of one or two (probably isomeric) radiochemical species. Exchange labelling at different pH values in the presence of stannous tartrate resulted in lower yields of the same 99mTc-labelled products as those formed during direct labelling. In addition, other radiochemical species were formed of which one was characterized as an oxotechnetium-complex with the cyclisized tetrapeptide. Tetrapeptides with a chiral centre in the first amino acid yield upon labelling with 99mTc two radiochemical species, probably the two diastereomers with an oxotechnetium core respectively syn and anti with respect to the substituent on the amino acid. Only one diastereomer was observed when the chiral carbon atom is located in the second or third amino acid. Electrophoresis indicated that these new 99mTc-labelled complexes are neutral in acidic medium and negatively charged in neutral and alkaline conditions. This correlates with a complex in which an oxotechnetium(V) group is bound to the ligand through three deprotonated nitrogen atoms of the amide functions and the free electron pair of the amine nitrogen atom. Biodistribution in mice showed for all studied 99mTc-labelled tetrapeptides a rapid clearance from the blood mainly by the renal system. The presence of a methyl substituent in the tetrapeptide increased the urinary excretion. 99mTc-labelledl -glycylalanylglycylglycine showed in mice a urinary excretion comparable to that of 99mTc-MAG3. Further rise of lipophilicity by introduction of a dimethyl, isopropyl or isobutyryl group leads to increased hepatobiliary handling. It is

Recently sup(99m)Tc-gluconate and sup(99m)Tc-dimercaptosuccinic acid (DMS) have been developed and used clinically as radiopharmaceuticals for renal scintigraphy. The author studied the renal uptake and body distribution of these two radio-pharmaceuticals experimentally using rats. A scinticamera equipped with a computer was utilized for dynamic curves in the clinical studies. sup(99m)Tc-gluconate was rapidly cleared from the blood and excreted in the urine. Renal uptake was rapid initially and then showed a gradual decrease. sup(99m)Tc-DMS, on the other hand, was slowly cleared and excreted. Renal uptake increased slowly and then levelled off. In clinical studies, sup(99m)Tc-gluconate provided valuable additional information about the renal collecting system in the early phase after injection. And the late scintigraphy with sup(99m)Tc-DMS was beneficial in demonstrating the kidneys of a patient with severe renal damage. Although some differences could be found in the distribution of these agents, both gave good renal images and seemed to be suitable radiopharmaceuticals for renal scintigraphy. (J.P.N.)

Aim: The aim of the present study was to evaluate the usefulness of dynamic scintigraphy in the assessment of total renal function in children. The Patlak slope of 99mTc-MAG3 renography curves were compared to the plasma clearance values of 51Cr-EDTA. Material and methods: The study sample consisted of 53 boys and 33 girls with various nephrologic disorders, referred for routine clinical reasons. The median age of the subjects was 5.1 years (range 0.3 - 14.1 years). Imaging procedure. In supine position, the patient received a bolus injection of 1 MBq/kg, (minimum 10 MBq) 99mTc-MAG3 and a posterior dynamic gamma camera registration was performed for 21 min using 1 frame per second during the first minute and thereafter 10 seconds frames. Data analysis. Time-activity curves were generated from manually drawn heart and renal regions of interest. The MAG3 uptake was calculated from the Patlak-Rutland plot of each kidney by linear curve fitting until the beginning of the excretory phase. A sum of the slope values was used as a measure of total renal MAG3 uptake. Cr-EDTA clearance. Glomerular filtration rate (GFR) was measured from the plasma clearance of 51Cr-EDTA using single injection, multiple-sample technique. After intravenous injection of 51Cr-EDTA (74 kBq/kg for children up to 7 years, 37 kBq/kg for children older than 7 years), blood samples were drawn at 5, 10, 15, 45, 60, 120 and 180 min for radioactivity measurement. The GFR was calculated according to Broechner-Mortensen and expressed in ml/min. Results: The absolute 51Cr-EDTA clearance varied from 9 to 143 ml/min. There was a close linear relationship between 51Cr-EDTA clearance and MAG3 uptake (Fig). The correlation coefficient was 0.90 and the regression equation (y=43.5 x + 664). Conclusions: In the present study, there was a good correlation between plasma clearance of 51Cr-EDTA and the sum of the Patlak slopes. The regression equation can be utilised to transform the 99mTc-MAG3 uptake to an estimate

The ''in vivo'' and ''in vitro'' studies on DISIDA -99mTc at the hepatobiliary level were made. The binding of DISIDA -99mTc to plasmatic proteins and the fraction at which this binding occurs were determined. The distribution coefficient in n-octanol/saline solution was 0.41 showing the lipophilicity of the compound. The images in rats show the biological distribution as well as the hepatobiliary clearance of the radiopharmaceutical under its unmetabolized form. (author)

Technetium-99m (99mTc) has emerged as the most widely used radionuclide in medicine and is currently obtained from a 99Mo/ 99mTc generator system. At present, there are only a handful of ageing reactors worldwide capable of producing large quantities of the parent isotope, 99Mo, and owing to the ever growing shutdown periods for maintenance and repair of these ageing reactors, the reliable supply 99mTc has been compromised in recent years. With an interest in alternative strategies for producing this key medical isotope, this thesis focuses on several technical challenges related to the direct cyclotron production of 99mTc via the 100Mo(p,2n)99mTc reaction. In addition to evaluating the 100Mo(p,2n)99mTc and 100Mo(p,x)99Mo reactions, this work presented the first experimental evaluation of the 100Mo(p,2n) 99gTc excitation function in the range of 8-18 MeV. Thick target calculations suggested that large quantities of cyclotron-produced 99mTc may be possible. For example, a 6 hr irradiation at 500 μA with an energy window of 18→10 MeV is expected to yield 1.15 TBq of 99mTc. The level of coproduced 99gTc contaminant was found to be on par with the current 99Mo/99mTc generator standard eluted with a 24 hr frequency. Highly enriched 100Mo was required as the target material for 99mTc production and a process for recycling of this expensive material is presented. An 87% recovery yield is reported, including metallic target preparation, irradiation, 99mTc extraction, molybdate isolation, and finally hydrogen reduction to the metal. Further improvements are expected with additional optimization experiments. A method for forming structurally stable metallic molybdenum targets has also been developed. These targets are capable of withstanding more than a kilowatt of beam power and the reliable production and extraction of Curie quantities of 99mTc has been demonstrated. With the end-goal of using the cyclotron-produced 99mTc clinically, the quality of the cyclotron

Technetium-99m 2-methoxy - isobutyl - isonitrile (99mTc-MIBI) has been reported to be useful in evaluating patients with multiple myeloma. The aim of this study is to evaluate the role of technetium-99m sestamibi (99mTc-MIBI) scintigraphy in the diagnosis. staging and follow-up of patients with multiple myeloma. Methods and Materials: twenty-five consecutive patients with multiple myeloma were studied using 99mTc- MIBI. Of the 25 patients included in this study, 6 were in stage I, II in stage II and 8 in stage III. Anterior and posterior whole-body imaging were obtained 20 min after I.V. injection of 740 MBq of 99mTc-MIBI. Four different MIBI patterns could be described in our patients: physiological (P), diffuse (D), focal (F) and combined diffuse and focal (D+F). All patients in stages II and III as well as 3 patients in stage I were treated with chemotherapy (cyclophosphamide and prednisone) then 99mTc-MlBI scans were repeated after 6 courses. Results: in comparison to conventional X-ray skeletal survey, 99mTc-MIBI scans showed a higher number of myeloma bone disease at diagnosis. All patients with stage II and III multiple myeloma were positive with 99mTc-MlBl scans at diagnosis. The pattern of positive MIBI accumulation was diffuse in 13 (52%) patients, focal in 4 (16%) and combined focal and diffuse in 6 (24%) patients. The intensity of 99mTc-MIBI correlated with disease activity as determined by lactate dehydrogenase (LDH), number of plasma cells in bone marrow and serum electrophoresis. There was a direct correlation between 99mTc-MIBI scan result and clinical outcome of patients following 6 courses of chemotherapy. Sensitivity and specificity of 99mTc-MIBI scintigraphy in detecting myeloma bone lesions were 92% and 90% respectively. Conclusion: 99mTc-MIBI scintigraphy is a reliable method to evaluate bone marrow activity in patients with multiple myeloma and follow-up of myeloma bone lesions

Samples of a culture of unlabeled Escherichia coli were incubated with different concentrations of stannous chloride for various time periods. 99mTc (26.0 MBq) was added to each preparation and the results showed a labelling yield of 98% for E. coli. Since the bacterial viability of 99mTc-E. coli and E. coli did not show any statistical differences, these results demonstrate that labelling of E. coli with 99mTc does not modify the bacterial viability, and the radiolabelled bacteria may be a good model to study bacterial translocation

DTPA clearance rate is a reliable index of alveolar epithelial permeability, and is a highly sensitive marker of pulmonary epithelial damage, even of mild degree. In this study, 99mTc-DTPA aerosol inhalation scintigraphy was used to assess the pulmonary epithelial membrane permeability and to investigate the possible application of this permeability value as an indicator of early alveolar or interstitial changes in patients with blunt chest trauma. A total of 26 patients was chest trauma (4 female, 22 male, 31-80 yrs, mean age; 53±13 yrs) who were referred to the emergency department in our hospital participated in this study. Technetium-99m diethylene triamine pentaacetic acid (DTPA) aerosol inhalation scintigraphy was performed on the first and thirtieth days after trauma. Clearance half times (T1/2) were calculated by placing a mono-exponential fit on the curves. Penetration index (PI) was calculated on the first-minute image. On the first day, mean T1/2 value of the whole lung was 63±19 minutes (min), and thirtieth day mean T1/2 value was 67±21 min. On the first day, mean PI values of the lung and 30th day mean PI value were 0.60±0.05, and 0.63 ±0.05, respectively. Significant changes were observed in radioaerosol clearance and penetration indices. Following chest trauma, clearance of 99mTc-DTPA increased owing to breakdown of the alveolar-capillary barrier. This increase in the epithelial permeability of the lung appears to be an early manifestation of lung disease that may lead to efficient therapy in the early phase. (author)

Background Bacterial infection can pose a substantial diagnostic dilemma.99mTc-labeled ciprofloxacin (CPF) was developed as a biologically active radiopharmaceutical to diagnose infection.In the present research,we studied the biodistribution and imaging properties of infection tracer 99mTc-CPF in a mouse model of infection.Methods CPF was labeled with 99mTc and the radiochemical purity and labeling rate were measured.A mouse model of infection was established.We then determined the biodistribution of 99mTC-CPF and conducted the whole body scintigraphy of the animal model.Results 99mTc-Ciprotech was stable for at least 6 hours at room temperature.The labeling rate of CPF by 99mTc was over 90%.Clearance of radioactivity mainly occurred in the liver and kidney,and the clearance from blood was rapid.Both biodistribution and imaging results showed higher uptake of 99mTc-CPF at sites of infection.The infectious tissue/normal tissue ratio peak was 4.30 at 4 hours after injection.Conclusions 99mTc-CPF is a sensitive radiopharmaceutical for scintigraphy of infectious lesions and it is easy to prepare.

Exogenous fibrinogen has been successfully labeled with /sup 99m/Tc using a modified electrolytic method. The exact labeling mechanism has not been determined. Experimental data suggest that the labeling process of /99m/Tc-fibrinogen is quite similar to that of /sup 99m/Tc-human serum albumin as reported earlier by Benjamin. Technetium-99m-fibrinogen is stable in human plasma or in 1 percent buffered human serum albumin. A binding efficiency of 76 percent has been achieved with approximately 25 percent clottable protein. The entire labeling procedure requires less than 1 hr of preparation time. This short labeling time in a closed system may allow development of a practical method for labeling autologous fibrinogen, thus eliminating the risk of hepatitis transmission. (U.S.)

The aim of this work was to prepare a kit of 99m Tc-ceftizoxime (99m Tc-CFT), with stability and biological activity preserved, able to identify a septic focus (E. coli) in the experimental infection model in rats. The preparation of the CFT kit involved the use of lyophilized solutions containing the antibiotic ceftizoxime and the sodium dithionite reducing agent (6.0 mg/m L). After lyophilization, the kit was reconstituted with 1.0 mL of sodium 99m Tc pertechnetate solution (Na 99m Tc O4-) with an activity of 370 MBq. The solution was boiled for 10 min and filtered through a cellulose ester filter. The labeling efficiency was on the order of 92%, remaining stable for six hours and the kit remained stable for two months. The biological activity of the 99m Tc-CFT was evaluated by diffusion in agar impregnated with E.coli and S. aureus. Seven Wistar rats, weighing from 200 to 250 g, were used for the development of the septic focus. After 24 hours from the induction of the infectious site (E.coli), the animals were anesthetized and 0.1 mL of 99m Tc-CFT (37 MBq) was injected into the tail veins of the animals. The images were obtained with a gamma camera one, two and six hours after injection and the regions of interest (ROIs) were calculated. The diameters of the inhibition halos for 99m Tc-CFT were 27.16 ± 0.23 and 27.17 ± 0.20 for S.aureus and E.coli, respectively, while those for the unlabeled CFT were 30.4 ± 0.33 and 29.43 ± 0.26, respectively. The results for the biodistribution of 99m Tc-CFT in infected animals furnished a ratio of 1.97 ± 0.31, 2.10 ± 0.42 and 2.01 ± 0.42 for cpm-target/cpm-no target for the one, two and six-hour periods, respectively. The images showed a clear uptake of labeled antibiotic (99m Tc-CFT) by the infectious site during the experiment. The results attest to the viability of producing a kit with 99m technetium-labeled ceftizoxime for the investigation of infectious processes. (author)

This study reports on the biodistribution and dosimetry of technetium-99m ciprofloxacin, a radio-ligand developed for the visualisation of bacterial infection. Whole body scans were performed up to 24 h after intravenous injection of 370 MBq 99mTc-ciprofloxacin in three male and three female volunteers. Blood samples were taken at various times up to 24 h after injection. Urine was also collected up to 24 h after injection, allowing calculation of renal clearance and interpretation of whole body clearance. Time-activity curves were generated for the thyroid, heart, liver and whole body by fitting the organ-specific geometric mean counts, obtained from regions of interest. The MIRD formulation was applied to calculate the absorbed radiation doses for various organs. The images showed rapid, predominantly urinary excretion of 99mTc ciprofloxacin, with low to absent brain, lung and bone marrow uptake and low liver uptake and excretion. Accordingly, imaging conditions are excellent for both the thoracic and the abdominal region, even at early time points (60 min) post injection. In none of the volunteers was the gallbladder visualised. Approximately 60% of the injected activity was recovered in urine by 24 h post injection. The highest absorbed doses were received by the urinary bladder wall, the thyroid, the upper large intestine, the lower large intestine and the uterus. The estimated mean effective dose for the adult subject, taking into account the weight factors of the ICRP60 publication, was 0.0083 mSv/MBq. The amount of 99mTc ciprofloxacin required for adequate planar and tomographic imaging results in an acceptable effective dose to the patient. (orig.)

This paper addresses the development of two new radiopharmaceuticals for imaging sites of infection. The optimization of the labeling yield of ciprofloxacin analogous, lomefloxacin and ofloxacin, with 99mTc was described. At ph 3.5 - 5 99mTc-lomefloxacin was obtained with a high radiochemical yield of 93.6 % by adding 99mTc to 2.5 mg lomefloxacin in the presence of 50 μ SnCl2 while 99mTc ofloxacin was obtained (96.6%) by adding 99mTc to 2 mg ofloxacin in tbe presence of 50μ g SnCl2. Biodistribution studies in rats were carried out in experimentally induced infection in the left thigh using Staphylococcus aureus. Both thighs of the rats were dissected and counted' and the ratio. of bacterial infected thigh/contralateral thigh was then evaluated. 99mTc-lomefloxacin showed higher uptake (T/NT = 6.5 ± 0.5) in the infectious lesion than 99mTc-ofloxacin (T/NT = 4.3 ± 0.6) and abscess-to-muscle ratios for both preparations were higher than that of 99mTc-ciprofloxacin (T/NT = 3.8 ± 0.8), indicating that 99mTc-lomefloxacin could be used instead of 99mTc-ciprofloxacin for imaging sites of infection

99mTc-EDDA/HYNIC-Tyr3-octreotide (99mTc-HYNIC-TOC) has shown high in vitro and in vivo stability, rapid background clearance and rapid detection of somatostatin receptor-positive tumors. The aim of this study was to establish a biokinetic model for 99mTc-HYNIC-TOC prepared from lyophilized kits, and to evaluate its dosimetry as a tumor imaging agent in patients with histologically confirmed neuroendocrine tumors. Whole-body images from eight patients were acquired at 5, 60, 90, 180 min and 24 h after 99mTc-HYNIC-TOC administration obtained from instant freeze-dried kit formulations with radiochemical purities >95%. Regions of interest (ROIs) were drawn around source organs on each time frame. The same set of ROIs was used for all eight scans and the count per minute (cpm) of each ROI was converted to activity using the conjugate view counting method. The image sequence was used to extrapolate 99mTc-HYNIC-TOC time-activity curves in each organ, to adjust a biokinetic model using the SAAM software, and to calculate the total number of disintegrations (N) that occurred in the source regions. N data were the input for the OLINDA/EXM code to calculate internal radiation dose estimates. Images showed an average tumor/blood (heart) ratio of 4.3±0.7 in receptor-positive tumors at 1 h. The mean radiation absorbed dose calculated for a study using 740 MBq was 24, 21.5, 5.5 and 1.0 mSv for spleen, kidneys, liver and bone marrow respectively and the effective dose was 4.4 mSv

Purpose: 18F-FDG glucose metabolic imaging plays an important role. in. clinical, practice. But, because of the expensive price of PET machine and cyclotron, 18F-FDG imaging is not easy to access and has difficult availability. Now the research of technetium labeled glucose is a hotspot in nuclear medicine imaging agent development. The Purpose of this study is to primarily study the clinical application in tumor imaging of 99mTc labeled glucose: 99mTc-EC-DG. Method: EC-DG was synthesized according to a known procedure (Yang et al, Radiology 226: 465, 2003). Labeling of 99mTc-ECDG was achieved by means of adding the required amount of ECDG and tin (II) chloride to the pertechnetate. Radiochemical purity was assessed at radio-thin-layer chromatography, with 1 mol/L of ammonium acetate plus methanol (4:1) as the eluant. 18 patients (9 cases of lung cancer, 1 lymphoma, 1 hepatic cell cancer, 1 recurrence of gastric cancer, 1 recurrence of thyroid cancer, 1 recurrence of colon cancer, 1 lung metastasis of thyroid cancer, 1 pneumonia, 1 tuberculosis and 1 inflammation of breast) fasted 6 hours and then underwent the 99mTc-EC-DG imaging after the injection of 25 mci 99mTc-EC-DG intravenously, the planar and tomographic imaging was acquired 2 hours and 4 hours after the injection, and the ratio of tumor to normal tissue was calculated. 4 of the 15 cases of malignant tumor were performed 18F-FDG imaging contrastively. The machine used in this study is Axis dual-headed coincidence SPECT of PICKER company, and iterative reconstruction is used in data process. Result: brain is not imaged and kidneys are clearly imaged in 99mTc-EC-DG imaging, the blood clearance of 99mTc-EC-DG is slower than that of 18F-FDG, the blood pool of heart and big blood vessel is seen at the time of 2 hours after the injection of 99mTc-ECDG, and still visible at 4 hours, the uptake of muscle is low. 14 cases of malignant tumor had positive imaging result (14/15), T/N ratio of 2 hours is 1.36-5.64 (2

Technetium-99m-labeled-5-{2-sulfanylethyl-[2-(2-sulfanylethylamino)acetyl] amino}-methyl-2'-deoxy-uridine (99mTc-ANMdU) was reported. The precursor ANMdU was synthesized by six-step reactions and all intermediates were verified with MS and 1HNMR. Using SnCl2 as reducing agent, a labeling reaction was carried out at 100 degree C for 30 min. The radiochemical purity of the 99mTc-ANMdU was 96.68%. Partition coefficients were 0.92 and 0.70 at pH 7.0 and 7.4 of the phosphate buffer saline, respectively. Biodistribution of 99mTc-ANMdU in normal mice showed that the initial uptake of 99mTc-ANMdU in vivo and the clearance was rapid. (authors)

99mTc-DTPA aerosol permeates the alveolar membrane by an intercellular pathway. Measurement of the clearance rate of 99mTc-DTPA aerosol is useful for assessing injury of the lung epithelium. Pertechnegas (P-gas) is also used to assess epithelial permeability, but its clearance is too rapid to evaluate lung epithelial permeability. The aims of this study were first to generate 99mTc-DTPA fine aerosol (D-gas), second to characterize D-gas by radiochromatography and an in vivo study in the rat, and third to investigate the clinical significance of D-gas in comparison with 99mTc-DTPA aerosol and P-gas. We generated D-gas in a chamber with an atmosphere of 3% oxygen and 97% argon inside the Technegas Generator. The clearance half-time of D-gas was 19.8±4.0 min in eight normal non-smoker subjects, 12.0±2.8 min in four smoker subjects, and 31±11.2 min in three with idiopathic interstitial pneumonia (IIP). In radiochromatography, the development of D-gas was the same as that of P-gas and different from that of 99mTc-DTPA solution. In the in vivo study using a rat, the distribution of intravenously injected D-gas solution was the same as that of 99mTcO4-, but different from that of 99mTc-DTPA solution. These results suggest that 99mTc-DTPA separates to free 99mTcO4- in the chamber of the Technegas Generator and that D-gas behaves in the same manner as P-gas. In conclusion, D-gas has no clinical significance for the assessment of epithelial permeability. (author)

Full Text Available The aim of this work was to prepare a kit of 99mTc-ceftizoxime (99mTc-CFT, with stability and biological activity preserved, able to identify a septic focus (E. coli in the experimental infection model in rats. The preparation of the CFT kit involved the use of lyophilized solutions containing the antibiotic ceftizoxime and the sodium dithionite reducing agent (6.0 mg/mL. After lyophilization, the kit was reconstituted with 1.0 mL of sodium 99mTc-pertechnetate solution (Na99mTcO4- with an activity of 370 MBq. The solution was boiled for 10 min and filtered through a cellulose ester filter. The labeling efficiency was on the order of 92%, remaining stable for six hours and the kit remained stable for two months. The biological activity of the 99mTc-CFT was evaluated by diffusion in agar impregnated with E.coli and S. aureus. Seven Wistar rats, weighing from 200 to 250 g, were used for the development of the septic focus. After 24 hours from the induction of the infectious site (E.coli, the animals were anesthetized and 0.1 mL of 99mTc-CFT (37 MBq was injected into the tail veins of the animals. The images were obtained with a gamma camera one, two and six hours after injection and the regions of interest (ROIs were calculated. The diameters of the inhibition halos for 99mTc-CFT were 27.16 ± 0.23 and 27.17 ± 0.20 for S.aureus and E.coli, respectively, while those for the unlabeled CFT were 30.4 ± 0.33 and 29.43 ± 0.26, respectively. The results for the biodistribution of 99mTc-CFT in infected animals furnished a ratio of 1.97 ± 0.31, 2.10 ± 0.42 and 2.01 ± 0.42 for cpm-target/cpm-no target for the one, two and six-hour periods, respectively. The images showed a clear uptake of labeled antibiotic (99mTc-CFT by the infectious site during the experiment. The results attest to the viability of producing a kit with 99m technetium-labeled ceftizoxime for the investigation of infectious processes.O objetivo deste trabalho foi preparar um kit de Tc

Health care reform truly has become a global issue and it will undoubtedly have a dramatic impact on the future of nuclear medicine business in particular. A bigger concern within the nuclear medicine community is its competitiveness with other modalities and cost effectiveness.Technetium-99m and its generators are playing key role for the majority of diagnostic scans performed in the world today. Availability of ''9''9''mTc can be increased if it is separated from ''9''9Mo after much shorter growth times. After proper planning with the extra ''9''9''mTc, a significant number of scans can be performed or we would be able to order approximately 30% low activity ''9''9Tc generators to fulfill our requirements

Aim: To study a distribution of Tc-99m MDP in mice bearing tumor cell lines. Methods: The uptake of Tc-99m MDP was analyzed in seven human tumor cell lines (SPC-A1 adenocarcinoma of lung cancer, P37 Breast cancer, T24 Bladder cancer, SKOV2 Ovary carcinoma, Hela-229 Cervical carcinoma, Osteosarcoma, A375 Melanoma) and one mouse lung cancer cell line (Lewis). They were transplanted into 13, 4, 5, 5, 4, 5 athymic mice, 6 SCID nude mice and 4 C57 black mice, respectively. Approximately 10(7) cells of each cell line were injected subcutaneously into a right chest of mouse. After 5∼6 weeks, the Tc-99m MDP scintigraphy were determined 5-6 hours after i.v. injection of 74MBq in 0.05ml every mouse. Result: Biodistribution and tumor uptake MDP was different in the various cell types investigated. Region of interests (RIOs) placed on a small part of the tumor and horizontal copied to left chest or spine of mice in Tc-99m MDP imaging and the average count ratio (tumor to background ratio: T/B, tumor to spine ratio: T/NT) in each ROI was calculated. 13 nude mice bearing the adenocarcinoma (SPC-A1) were sacrificed and biodistribution was determined after Tc-99m MDP scintigraphy. Results were expressed as % injected dose/gram (%ID/g), mean±SD. T-ulcer=ulcer of tumor, T-round=surrounding of tumor, T-center=the center of tumor, Thor-sp=thoracic spine, Lum-ver=lumbar vertebra, LN=lymph node. Conclusions: Tumor can uptake Tc-99m MDP including adenocarcinoma. Higher uptake rate in the center tissue of tumor is than other part of tumor. It maybe connected with necrosis or fibrosis of tumor

Full text: At the last years special attention is paid on reception and use of radiopharmaceutical preparation on the basis of 99mTc radioisotope. 99mTc is the most widely used radioisotope in nuclear medicine for today. Usually 99mTc radioisotope is received from its generator, in which as a parent radioisotope serves 99Mo. In the system, 99mTc and 99Mo radioisotopes are found in genetic balance and certain time interval, 99mTc radioisotope is separated from the system by chemical way. There are many ways of manufacturing and variants of the 99mTc generators. Nevertheless, investigators do not stop to search new methods of generator system. One of such methods can appear tube generators based on solid insoluble salts of Molybdenum with radioactive 99Mo. Such salts in our experiments were used molybdates Barium, Calcium and phosphorus molybdate Cesium. Here we present the solubility product of the specified salts: BaMoO4 - 4.10-8, Ca MoO4 - 4,7.10-9, Cs3 [P (Mo3O10)4] - 1,7.10-11. Salts of Barium and Calcium have been received by inclusion of 99Mo radioisotope into the chemical structure of salts at a stage of their synthesis by mixing solutions containing Ba+2, Ca+2 and 99MoO4-2 ions. Phosphorus molybdate Cesium has been received by mixing solutions containing Cs- and phosphorus molybdate (99Mo) - ions. The basic parameter of radioisotope generators is yield of daughter radioisotope from system. This parameter appeared to be equal to 77,6% in case of Phosphorus molybdate Cesium, 75,2% in case of molybdate Calcium and 70,8% in case of molybdate Barium. Preliminary results show that researches in this field can be continued

This study was designed to evaluate the usefulness of a technetium-99m mercaptoacetyltriglycine (Tc-99m MAG3) single photon emission computed tomography (SPECT) performed on transplanted kidney. Thirty renal transplant patients were included in this study. Planar scan was performed for 30 minutes using 555 MBq Tc-99m MAG3. A post-voiding SPECT scan was acquired on the third, seventh, fourteenth and twenty eighth day after transplantation. SPECT scan showed interpretable image quality in 26 of 30 patients (86.7%) and 84 in 120 scans (70%). Fourteen of 26 patients with interpretable SPECT image showed decreased or increased radioactivity, but only 5 had abnormal findings on the planar scan. Focal SPECT defects were seen in allografts with normal function (n=3), acute tubular necrosis (n=3), and acute rejection (n=2). The defects are thought to reflect focally underperfused renal parenchyme or, in normal allografts, an artifact from uneven radioactivity distribution. Four of 10 paints with renal arterial variation showed focally decreased radioactivity and SPECT helped guide further studies that confirmed the exact cause. Five of 10 patients with acute tubular necrosis or acute rejection showed focally decreased radioactivity, but its relation to the patients' clinical course was not clear. Focally increased radioactivity was observed in 5 allografts with normal function and 1 with double ureter in which local clearance delay was observed. Tc-99m MAG3 SPECT renal scan can detect additional focal abnormalities compared to planar scan. Further study is necessary to elucidate the exact clinical significance of the SPECT findings.

This study was designed to evaluate the usefulness of a technetium-99m mercaptoacetyltriglycine (Tc-99m MAG3) single photon emission computed tomography (SPECT) performed on transplanted kidney. Thirty renal transplant patients were included in this study. Planar scan was performed for 30 minutes using 555 MBq Tc-99m MAG3. A post-voiding SPECT scan was acquired on the third, seventh, fourteenth and twenty eighth day after transplantation. SPECT scan showed interpretable image quality in 26 of 30 patients (86.7%) and 84 in 120 scans (70%). Fourteen of 26 patients with interpretable SPECT image showed decreased or increased radioactivity, but only 5 had abnormal findings on the planar scan. Focal SPECT defects were seen in allografts with normal function (n=3), acute tubular necrosis (n=3), and acute rejection (n=2). The defects are thought to reflect focally underperfused renal parenchyme or, in normal allografts, an artifact from uneven radioactivity distribution. Four of 10 paints with renal arterial variation showed focally decreased radioactivity and SPECT helped guide further studies that confirmed the exact cause. Five of 10 patients with acute tubular necrosis or acute rejection showed focally decreased radioactivity, but its relation to the patients' clinical course was not clear. Focally increased radioactivity was observed in 5 allografts with normal function and 1 with double ureter in which local clearance delay was observed. Tc-99m MAG3 SPECT renal scan can detect additional focal abnormalities compared to planar scan. Further study is necessary to elucidate the exact clinical significance of the SPECT findings

Three methods for evaluating relative renal function in a pediatric population were compared. The clinical and nuclear medicine data of 73 patients were reviewed. Pertinent data included patient age, serum creatinine and the referral diagnosis (reflux, hypertension, obstructive uropathy). Time activity curves for renal regions of interest (ROI) were obtained by renography with Tc-99m DTPA, and deconvolved by an externally detected blood pool curve Furosemide was then administered to evaluate the renal collecting system (if indicated). This was followed by DMSA administration. Relative function was determined in 3 ways: 1) Accumulated renal DTPA activity 60-120 sec. following injection. 2) Amplitude of the tubular phase of the deconvolved renal curve and, 3) Accumulated Tc-99m DMSA activity in renal ROI 4 or 24 hrs. post-injection. Regression analysis revealed: 1) The basic relationship of relative functional data obtained by all three methods was not affected by creatinine, age or other factors. 2) The relationship between the three methods is linear and highly correlated. 3) The DMSA values may be predicted from either method of analyzing the DTPA study using appropriate predictor equations. The authors conclude that Tc-99m DMSA, due to its higher cost and more radiation exposure should not be used for the routine evaluation of relative renal function.

Renal uptake of 99m Tc DMSA was used to evaluate the renal function of 16 healthy subjects (controls) and 115 patients with various urinary tract diseases. Scintigraphic examination was carried out 6 hours after an intravenous injection of the product. In the 16 controls Tc DMSA uptake was 25.7+-2.48% in the right kidney and 24.4+-2.86% in the left kidney. In 36 patients with one single hypertrophied kidney, there was a correlation (r=0.850) between creatinine clearance and Tc DMSA uptake, which was higher than in normal subjects (39.23+-9.9%). In the group of 68 patients with unilateral (31) or bilateral (37) renal disease, a significant correlation (r=0,725) was observed between kidney-to-kidney ratios of urea clearance and Tc DMSA uptake, so that renal impairment could be quantified. Quantitative scintigraphy did not appear to be of assistance in the remaining 11 patients with obstructive uropathy, as it overestimated renal function. The results obtained with 99m Tc DMSA scintigraphy should be helpful in choosing between nephrectomy and conservative surgery and in assessing the degree of compensatory hypertrophy in single kidneys

The uptake characteristics of technetium-99m hexakis-2-methoxyisobutylisonitrile (MIBI), {sup 99m}Tc-tetrofosmin and {sup 99m}Tc-furifosmin in human soft tissue sarcoma cell lines were investigated and compared. After 10-120 min of incubation at 37 C, 32 C and 22 C with {sup 99m}Tc-MIBI, {sup 99m}Tc-tetrofosmin and {sup 99m}Tc-furifosmin, the kinetics of cellular uptake of these tracers in human soft tissue sarcoma cells SW 684 (fibrosarcoma), SW 872 (liposarcoma), SW 982 (synovial sarcoma) and SW 1353 (chondrosarcoma) was assessed. The uptake of {sup 99m}Tc-MIBI, {sup 99m}Tc-tetrofosmin and {sup 99m}Tc-furifosmin was temperature dependent. The kinetics of uptake of {sup 99m}Tc-MIBI and of {sup 99m}Tc-tetrofosmin was similar between fibrosarcoma and liposarcoma cells, as well as between synovial sarcoma and chondrosarcoma cells. {sup 99m}Tc-furifosmin showed similar uptake kinetics in all cell lines. The uptake of {sup 99m}Tc-furifosmin was, however, significantly higher in liposarcoma than in the other cells. The data indicate that the cellular uptake of {sup 99m}Tc-MIBI, {sup 99m}Tc-tetrofosmin and {sup 99m}Tc-furifosmin is dependent on cellular metabolic activity. (orig.)

The uptake characteristics of technetium-99m hexakis-2-methoxyisobutylisonitrile (MIBI), 99mTc-tetrofosmin and 99mTc-furifosmin in human soft tissue sarcoma cell lines were investigated and compared. After 10-120 min of incubation at 37 C, 32 C and 22 C with 99mTc-MIBI, 99mTc-tetrofosmin and 99mTc-furifosmin, the kinetics of cellular uptake of these tracers in human soft tissue sarcoma cells SW 684 (fibrosarcoma), SW 872 (liposarcoma), SW 982 (synovial sarcoma) and SW 1353 (chondrosarcoma) was assessed. The uptake of 99mTc-MIBI, 99mTc-tetrofosmin and 99mTc-furifosmin was temperature dependent. The kinetics of uptake of 99mTc-MIBI and of 99mTc-tetrofosmin was similar between fibrosarcoma and liposarcoma cells, as well as between synovial sarcoma and chondrosarcoma cells. 99mTc-furifosmin showed similar uptake kinetics in all cell lines. The uptake of 99mTc-furifosmin was, however, significantly higher in liposarcoma than in the other cells. The data indicate that the cellular uptake of 99mTc-MIBI, 99mTc-tetrofosmin and 99mTc-furifosmin is dependent on cellular metabolic activity. (orig.)

Introduction: 99mTc-TMEOP is a novel heart perfusion radiotracer exhibiting high initial and persistent heart uptake associated with rapid blood and liver clearance. This study aimed at determining the mechanisms of myocardial localization and fast liver clearance of 99mTc-TMEOP. Methods: Subcellular distribution of 99mTc-TMEOP was determined in excised rat heart tissue by differential centrifugation. The effect of cyclosporin A on the pharmacokinetic behaviour of 99mTc-TMEOP was evaluated by both ex vivo biodistribution and in vivo planar imaging studies. Results: Subcellular distribution studies showed that more than 73% of 99mTc-TMEOP was associated with the mitochondrial fraction. Comparison with subcellular distribution of 99mTc-sestamibi showed no significant difference in the mitochondrial accumulation between the two tracers. Biodistribution studies in the presence of cyclosporin A revealed an increase in kidneys and liver uptake of 99mTc-TMEOP, suggesting the involvement of multidrug resistance transporters in determining its pharmacokinetic profile. Conclusions: The heart uptake mechanism of 99mTc-TMEOP is similar to that of the other reported monocationic 99mTc cardiac agents and is associated with its accumulation in the mitochondria. Cyclosporin A studies indicate that the fast liver and kidney clearance kinetics is mediated by P-glycoprotein (Pgp), supporting the potential interest of this radiotracer for imaging Pgp function associated with multidrug-resistant tumours.

Gentamicin sulphate is an aminoglycoside antibiotic type specifically used for treatment of infections produced by Gram-negative bacterias but at the other hand it presents ototoxic reactions as a serious side effect. The main purpose of labelling gentamicin with sup(99m)Tc was to obtain a radioactive tracer to carry out biological studies and compartmental analysis of this antibiotic. The optimal labelling conditions of gentamicin sulphate with sup(99m)Tc, using sodium pertechnetate solution eluted from a sup(99)Mo- sup(99m)Tc generator, were stablished by testing different masses of antibiotic, and reduction agent (SnCl sub(2).2H sub(2)O), and also different reaction time and final labelling PH. The same labelling procedure was used with Re (amonium perrenate) in order to obtain some semi-quantitative approximations of the chemical structure of the complex formed, since Re and Tc present similar chemical characteristics. In this way it is possible to suggest the role that the groups NH2 and C-O bonding of the gentamicin play in the complexation process. From the studies of the biological uptake of sup(99m)Tc-gentamicin sulphate in rats, the kidneys showed the highest affinity for the antibiotic. The maximum uptake was observed in 180 to 240 minutes followed by a decrease of it afterwards. For the dose and time used, no significative uptake by the auricular region was detected. Curve of plasma decay of sup(99m)Tc-gentamicin was obtained, and from the exponentials of each beanch of this curve respective half-lives were calculated. Furthermore the apparent volume of distribution was determined, and with the residual radioactivity in the body, the biological half-life and total clearance were obtained. The distribution of sup(99m)Tc-gentamicin in rats was set in a bi-compartments in addition to a retention one for the 24 hours time interval studied. (author)

121 patients suspected of breast cancer were studied with MIBI-99mTc to evaluate the suitability of the mammary scintigraphy in patients with doubtful cancer diagnosis.The results show 93 % sensitivity and 95 % specificity and indicate the usefulness of this procedure to increase the accuracy of the diagnosis

The role played by technetium-99m generators in diagnostic medicine, their physical and chemical fundamentals and their main technical characteristics are discussed. This report is intended as a general introduction to a group of reports which summarize the work done on the development and production of the generators, and research on the chemical and physical aspects of the generator systems

The technetium-99m generator is one of the main products of the PPR, as the continuity of the technetium-99m generator production is important for supporting the development of nuclear medicine. GENTC99M has been made for computational for the technetium-99m generator and includes data processing, documentation and information GENTC99M is also very useful in quality control application especially for the determinations of yield and radionuclidic impurities which consume much time. microsoft visual basic for MS-DOS and visual basic for windows have been used for making GENTC99M. Microsoft visual basic has several features that make it an ideal development language for both MS-DOS and Microsoft Windows. These features not only increase productivity, they also provide all the tools and hooks needed to develop some very sophisticated applications. for a production centre like PPR, GENTC99M is very useful to support the data processing, documentation and information system of the technetium-99m generator and it can also be modified for other products

Aim: Tc-99m ciprofloxacin (Infecton) imaging was developed to discriminate infection from inflammation. It claims to show an area of viable, proliferating bacterial population that is actively using DNA gyrase, which the ciprofloxacin inhibits. The application of this imaging has been reported in patients with infected arthroplasty, soft tissue infection, pelvic inflammatory diseases, etc. Clinical evaluation with conventional urological laboratory tests often provides insufficient data in differentiating chronic bacterial prostatitis (CBP) from pelvic pain syndrome, which causes inappropriate or inadequate antibiotic therapy without definite evidence of presence or absence of bacterial infection. Therefore, we investigated the diagnostic value of the Tc-99m ciprofloxacin imaging for CBP by comparing the results of the imaging with those from the conventional tests. Materials and Methods: We custom-formulated a Tc-99m ciprofloxacin kit. We used stannous tartrate for a reducing agent in making the kit. SPECT images of the region of interest were obtained at 3 hours after injection of the radiopharmaceutical. For positive control, we imaged 2 patients: acute prostatitis and urethritis. Then the actual study included 20 subjects. We excluded from the study the patients who had received antibiotic therapy within 6 weeks. The conventional tests included CBC, urinalysis, 4-glass tests, microscopic examination of expressed prostatic secretion, bacterial culture, or PCR for chlamydia trachomatis. Kappa statistics were obtained for comparison of the two tests. Results: By conventional tests, there were 10 subjects with CBP and 10 normal subjects. The typical pattern in the Tc-99m ciprofloxacin imaging indicating CBP was the increased uptake around the prostatic urethra. Five of the 10 subjects with CBP diagnosed by conventional tests showed the increased uptake to be positive cases in the Tc-99m ciprofloxacin imaging. Of the 10 subjects diagnosed as normal by the

Objective: To study the distribution of 99mTc-MDP in mice bearing tumor cell lines. Methods: The uptake of 99mTc-MDP was analyzed in seven human tumor cell lines (SPC-Al adenocarcinoma of lung cancer, Bcap-37 breast cancer, T-24 bladder cancer, SKOV3 ovary carcinoma, Hela-229 cervical carcinoma, SCI-OS osteosarcoma, SCI-375 melanoma) and one mouse lung cancer cell line (Lewis). They were transplanted into athymic mice, SCID and C57 mice, respectively. Approximately 10(6) cells of each cell line were injected subcutaneously into a right chest of mouse. After 5-6 weeks, Tc-99m MDP scintigraphy were performed 5-6 hours later after i.v. injection of 74 MBq in 0.05 ml in every mouse. Results:Biodistribution and tumor uptake of MDP was different in the various cell types investigated. Region of interests (ROIs) were placed on a small part of the tumor and a horizontal copied to left chest or spine of mice in Tc-99m MDP imaging. The average count ratio (tumor to contralateral tissue ratio: T/L, tumor to spin ratio: T/N) was calculated. Conclusions: Tumor can uptake Tc-99m MDP including adenocarcinoma. Uptake rate in the central tissue of tumor is higher than other parts of tumor. It may be connected with necrosis calcification of tumor. Tumor or acute myocardial infarction uptake of bone scanning agent may follow the sequence: anoxia-necrosis- calcium and phosphorus ions deposition

A reliable method for measuring lymph flow in physiological units would be valuable, especially in conditions in which it is uncertain whether lymph flow is increased or decreased. The requirements of a radiopharmaceutical for such measurement include stable radionuclide labelling and rapid access to lymphatic vessels following tissue injection but no access to blood vessels. A soluble macromolecule is likely to come closest to meeting these requirements. Technetium-99m- labelled human polyclonal immunoglobulin (HIG) was therefore investigated firstly in comparison with 99mTc-labelled human serum albumin (HSA) in patients undergoing routine lymphoscintigraphy and secondly with respect to injection site in a group of volunteers with post-mastectomy oedema (PMO). Subcutaneous injection of 99mTc-HIG into the web space of a distal extremity gave images in which lymphatic vessels were more clearly defined compared with images obtained after injection of 99mTc-HSA. Lymph nodes were also more clearly defined, suggesting specific retention of HIG, possibly through Fc-mediated binding. Peripheral blood sampling showed a delayed arrival in blood of radioactivity after 99mTc-HIG compared with 99mTc-HSA, although ultimately, the blood recovery of 99mTc-HIG was significantly higher (P 99mTc-HSA. Clearance rates of radioactivity from the injection site were not sinificantly different, however, between the two agents. In patients with PMO, web space injection of 99mTc-HIG gave excellent images of normal lymphatic vessels, of lymph nodes and of abnormal lymph drainage such as dermal backflow in swollen arms. In contrast, neither lymphatic vessels nor lymph nodes were visualised after injection into the skin of the dorsum of the distal forearm. Although there was no difference in clearance rates from the injection sites between normal and swollen arms with either agent in PMO, clearance was significantly faster following injection into the web space (0.11% per minute for normal and

The purpose of the study was to compare the estimation of glomerular filtration rate (GFR) from 99mTc-DTPA renography with that estimated from the renal clearance of 51Cr-EDTA, creatinine and urea.......The purpose of the study was to compare the estimation of glomerular filtration rate (GFR) from 99mTc-DTPA renography with that estimated from the renal clearance of 51Cr-EDTA, creatinine and urea....

The pulmonary clearance of aerosol DTPA-Tc99m is a technology easy to use, well support by patients with immediate results. With the pneumonia at Pneumocystis Carinii (PPC), the clearance is more sensitive and more specific than the thoracic scintigraphy with Ga67. Used with a thorax radiography, results will lead to three directions: High probability of PPC, di phasic curve and very fast T50, equal inferior to 5,10 mn. Low probability of PPC, monoexponential curve and abnormal thorax radiography or di phasic curve with a value T50 superior to 5,10 mn. With these patients other explorations will be made (Ga67, biopsy) and if possible search pulmonary tuberculosis. Extra pulmonary pathology: monoexponential curve associated with a normal thoracic radiography. 2 figs.

Clearances of inulin, 125I-iothalamate, and /sup 99m/Tc-Sn-DTPA were measured simultaneously in five mongrel dogs exhibiting a wide range of glomerular filtration rates (GFR). Standard constant-infusion inulin clearance was compared to radionuclide clearances after subcutaneous injection of the emitters mixed with aqueous epinephrine. All three substances were found to have virtually identical clearances. The accuracy, accessibility, low cost, low radiation hazard, and short half-life of /sup 99m/Tc-Sn-DTPA make it an excellent substance for measuring GFR. The subcutaneous technique offers an accuracy comparable to the more difficult constant-infusion method

Previous investigators, using 99mTc-DTPA aerosol as a marker to assess epithelial permeability in asthma, did not find an increased permeability in this group. However, they either failed to deliver the aerosol to the optimal site (bronchial mucosa, not alveoli) or failed to account for mucociliary clearance in analyzing their results. We studied 10 asthmatics and eight age-matched control subjects using a dosimeter (Spira-Elektra 2) and a carefully controlled breathing pattern to deliver aerosol to the subjects' airways. Two aerosols were delivered on separate days in each patient; 99mTc-DTPA aerosol, and 99mTc-HSA (human serum albumin), using similar breathing patterns to ensure reproducibility of the deposition pattern with the two aerosols. From measurements of retention versus time over a 1-h period, rate constants Ktot and Km were determined for the clearance of 99mTc-DTPA and 99mTc-HSA, respectively. By modelling the airways as a single compartment with two possible routes of clearance, we determined the permeability rate constant, Kp, as Ktot minus Km. There was no significant difference between Ktot in normal subjects and asthmatics; however, because of the slower mucociliary clearance in the asthmatic group, and the relative importance of mucociliary clearance in determining the washout of 99mTc-DTPA aerosol, there was a significant difference in airway permeability between the normal subjects and the asthmatics (t1/2 = 296 min +/- 141 SD and 126 min +/- 58, p less than 0.01, in normal subjects and asthmatics, respectively)

Purpose: To evaluate the role of combined high resolution ultrasonography and technetium Tc-99m methoxyisobutylisonitrile (MIBI) parathyroid scintigraphy in preoperative detection and localization of parathyroid adenoma, for better operative outcome. Patients and methods: 40 patients were included in this study, 25 of them were females and 15 were males, with age ranging between 31 and 75 (mean 46 ± 15). All patients presented with some of symptoms of hyperparathyroidism with venous blood ...

A major focus of cardiovascular radiopharmaceutical research over the past decade has been the search for a Tc-99m agent that could replace Tl-201, the current agent of choice for myocardial perfusion imaging. Recent advances in the inorganic chemistry of technetium, and in the translation of this chemistry to radiopharmaceutical development, make it very likely that this search will soon be successfully completed

Diabetic nephropathy is the most common cause of end stage renal disease and the incidence is progressively increasing. The aim of this study was to investigate the differences of {sup 99m}Tc-DMSA renal uptake among diabetic patients with normoalbuminuria, microalbuminuria and overt proteinuria, and then to determine the clinical usefulness of {sup 99m}Tc-DMSA in predicting early diabetic nephropathy. {sup 99m}Tc-DMSA scan was performed and a total renal uptake of {sup 99m}Tc-DMSA was measured in 145 diabetic patients. Patients were divided into 3 groups according to the amount of 24 hour urinary albumin excretion as Group I (normoalbuminuria, 74 cases ), Group II (microalbuminuria, 39 cases), and Group III (overt proteinuria, 32 cases). The differences of {sup 99m}Tc-DMSA renal uptake among the 3 groups and the correlation between the renal uptake of {sup 99m}Tc-DMSA and other clinical parameters were analyzed. The total renal uptake of {sup 99m}Tc-DMSA of Group II (40.8{+-}11.0%) was significantly lower than that of Group I (54.4{+-}6.3%, p<0.001). The uptake of Group III (27.7{+-}12.0%) was significantly lower than those of both Group I and Group II (p<0.001). {sup 99m}Tc-DMSA total renal uptakes correlated negatively with serum creatinine level (r=0.629, p<0.001) and positively correlated with creatinite clearance rate (r=0.702, p<0.001). {sup 99m}Tc-DMSA total renal uptake of diabetic patients with microalbuminuria was significantly decreased compared with that of patients of normoalbuminuria. Therefore, {sup 99m}Tc-DMSA scan can be used as a diagnostic study for early detection of the diabetic nephropathy.

Quality control (QC) studies of three locally produced renal preparation of 99mTc-DTPA, 99mTc-GH and 99mTc-DMSA, as a part of the production activity before the Gulf war. The radioanalytical studies were performed using Gel Chromatography column Scanning (GCS) technique, although there are other alternative techniques. These kits tested for radiochemical purity and the labeling yields were found to be excellent. The biological studies included the following parameters; organ distribution (in mice, rats and rabbits), blood clearance in rabbits and plasma protein binding in rats at different time intervals. The poor renal concentration of three agents in mice was significant at two time intervals . The tissue distribution of DTPA, GH and DMSA kits, which were stored at 37 OC for 30 days in mice after intravenous injection of the radioactivity at 5, 30 and 60 minutes. The blood retention of the renal agents was considerably low compared to those in rats and rabbits at the respective time intervals. The blood clearance of 99m'Tc-DMSA was relatively slow and 99mTc-GH has rapid blood clearance identical with that of 99mtc-DTPA for the first 20 minutes but slower thereafter. The binding of DTPA, GH and DMSA with plasma protein was 5, and 95% at 1 hour respectively. Various amounts of tin (11) (as SnCl-2) were used in the kits with up to 10 times more of the usual dose for respective tin-complex and it was observed that there was no significant variation of the usual dose for respective tin-complex and its was observed that there was no significant variation of the organ distribution in mice. (Author)

Full text: Evaluation of the role of scintigraphy with 99mTc-Sestamibi (99mTc-MIBI) and 99mTc-Tetrofosmin (99mTc-TF) in the detection of bone marrow involvement in patients (pts) with multiple myeloma (MM) and in follow-up. 62 pts with MM and 38 pts with monoclonal gammopathy of undetermined significance (MGUS) were enrolled in this study. Forty-seven out sixty-two MM pts had active disease (AD), 10/62 were in complete remission (CR) and 5/62 in partial remission (PR) after chemotherapy. Whole-body scans were obtained 10 min after the i.v. injection of 740 MBq of 99mTc-MIBI in anterior and posterior view. The scans were scored semiquantitatively according to extension and intensity of tracer uptake. All 38 MGUS pts had a negative 99mTc-MIBI scan. As to the MM pts, 49/62 pts (44 with AD, 4 with PR and 1 with CR) had a positive 99mTc-MIBI scan, while the 99mTc-MIBI scan was negative in 13/62 pts (9 with CR, 1 with PR and 3 with AD). The overall sensitivity of the scintigraphic procedure was 92 % while specificity was 97 %. A total of 42 follow-up scans with 99mTc-MIBI were performed in 30 MM pts after high-dose chemotherapy, with an average follow-up duration of 14.6 ± 8.9. The follow-up 99mTc-MIBI scintigraphy was positive in 14/15 of the AD pts, while 6/8 negative scans were observed in the CR pts; the seven PR pts exhibited in five cases a negative scan and in two a mild scintigrafic positivity. The overall sensitivity and specificity of the follow-up scan were, respectively, 86 % and 75 %. In six patients, one at the diagnosis and five showing a positive 99mTc-MIBI scan during the follow-up, 740 MBq of 99mTc-TF was administered within two days with the same acquisition protocol. The scans provided substantially identical information. 99mTc-TF provided a mildly higher contrast between lesion and background activities. The results obtained in this study provide additional evidence indicating that 99mTc-MIBI scintigraphy closely reflects myeloma disease activity in

Liver scintigraphy using 99mTc-galactosyl human serum albumin (GSA), which binds specifically to the asialoglycoprotein receptors on the surface of the hepatocytes, was performed in 41 patients with chronic liver disease (11 chronic hepatitis cases and 30 liver cirrhosis cases) to investigate the correlations between the images and the various liver function tests. Two liver functional indexes, HH15 for plasma clearance of 99mTc-GSA and LHL15 for liver accumulation of 99mTc-GSA, showed significant differences between the chronic hepatitis group and the decompensated liver cirrhosis group. These indexes also showed significant correlations with the liver function tests such as serum albumin level and prothrombin time. HH15 and LHL15 correlated with the per-rectal portal shunt index obtained in 10 patients by 99mTcO4- per-rectal portal scintigraphy. These results suggest that HH15 and LHL15 have value as new liver functional indexes. (author)

To explore the mechanism of technetium-99m-methylene diphosphonate (MDP) uptake within tumor through analyze a distribution of Tc-99m MDP in mice bearing tumor cell lines. Methods: The uptake of Tc-99m MDP was analyzed in seven human tumor cell lines ( SPC-A1 adenocarcinoma of lung cancer, Bcap-37 Breast cancer, T-24 Bladder cancer, SKOV3 Ovary carcinoma, Hela-229 Cervical carcinoma, SCI-OS Osteosarcoma, SCI-375 Melanoma) and mouse Lewis lung cancer cell line. They were transplanted into athymic mice, SCID nude mice and C57BL/6 mice, respectively. Approximately 10(6) cells of each cell line were injected subcutaneously into a right chest of mouse. After 4 and 5 weeks, the Tc-99m MDP scintigraphy were determined 6 hours after tail vein injection of 74MBq in 0.05ml every mouse. Result: Biodistribution and tumor uptake MDP was different in the various cell types investigated. According to the Region Ratio program of Siemens Power Macintosh 9500 Computer System, region of interests (RIOs) placed on a small part of the tumor and horizontal copied to left background (T/B) and thoracic spine (T/N) of mice in Tc-99m MDP imaging. The average cpm/pixel ratios were calculated by standardized uptake measure (SUM) and determined the tumor-positive value (T/B) greater than or equal to 1.2. T/B of cell lines were sorted from higher to lower as follows: SCI-OS, Lewis, SKOV3, SCI-375, T-24, SPC-A1, Bcap-37, Hela-229. T/N: SCI-OS, SKOV3, T-24, SCI-375, Lewis, SPC-A1, Bcap-37, Hela-229. The biodistribution data of 99Tcm-MDP in SPC-A1 tumor-bearing BALB/c nude mice were given as ID/g and represent the means D (n=13) in 30 hours after injection of Tc-99m MDP. ID/g of major tissue were sorted from higher to lower as follows: thoracic spine, lumbar, ribs, kidneys, the center of tumor, the ulcer of tumor, the surrounding of tumor, lymph node, blood, lungs, heart, liver. Conclusions: Most of tumor can uptake Tc-99m MDP including human adenocarcinoma. The uptake rate in the center tissue of

Amphotericin B (AMB) with a broad spectrum of antifungal activity is used for the treatment of life-threatening mycoses, especially in immunocompromised patients. Since measurements of the blood level of AMB and of creatinine do not provide early warning of AMB induced renal toxicity, we studied the effects of AMB on biodistribution of a glomerular agent, 99mTc-DTPA. In Swiss mice, the toxicity of AMB was studied at single intravenous doses of 0.5-3.5 mg/kg body weight. Dose dependent effects consisted of decreased blood clearance and urinary excretion. Recovery of function was shown in dose ranges corresponding to high level clinical schedules. Serum creatinine changes lagged behind the99m Tc-DTPA alterations. This suggests that AMB toxicity might be monitored by blood/urinary clearance of 99mTc-DTPA

The ligand carboxymethylthioethyl iminodiacetic acid (CMT-IDA), an analogue of nitrilotriacetic acid (NTA) has been radiolabeled with technetium-99m to study its renal clearance and determine its potential as a renal tubular imaging agent. (99mTc(CO)3CMT-IDA)2- could be obtained in >98% radiochemical purity as determined by HPLC. Stability, hydrophilicity and plasma protein binding studies were carried out and were found to be comparable to that of (99mTc(CO)3NTA)2-. Biodistribution studies were carried out in normal Swiss mice at 10 min. p.i. and 2 h.p.i. The complex has shown renal clearance of (71.0±5.9)% ID at 10 min. p.i., which increased to (84.1±10.6)% at 2 h.p.i., with no major uptake in vital organs. (author)

Dry-kit methods to label DTPA with 99mTc were evaluated. Quality control of 99mTC-DTPA was performed with two gel chromatography methods. The gel chromatography scanning methods was the only method that resulted in a satisfactory separation of the various components. A reproducible high labeling yield of 99mTc-DTPA was found to result. No difference as to the occurrence of vesicoureteral reflux could be established between 99mTc-DTPA and X-ray cystouretherography. Renograms obtained with simultaneously administered 99mTc--DTPA and 131I-Hippuran were compared. The Spearmans correlation coefficients were rs greater than or equal to 0.61 (P less than 0.0005) for normal kidneys. The renogram curves were very similar but not identical in both normal and pathological kidneys. The use of a stochastic modeel and deconvolution enabled renal retention curves to be calculated. The following data were evaluated from the curves: AMPLITUDE of the plateau, MAXIMUM TIME, and MEAN TRASIT TIME. The values obtained with 99mTc-DTPA and 131I-Hippuran correlated well. With both tracers it was possible to distinguish three groups: Normal, parenchymal insufficiency, and ureteral obstruction. Since retention curves express the renal function in its simplest and most explicit form, such curves are easier to interpret than conventional renograms. (author)

111In-tropolonate-granulocytes (G-111In) study was performed in 16 patients with inflammatory bowel disease (IBD). Images were obtained 3 h and 20 h post-injection. Counting of four days feacal excretion was more accurately expressed as daily intestinal granulocytes clearance. The day before, 12 of the patients had a sucralfate-99mTc scan (S-99mTc). Correlation between radioendoscopic data and S-99mTc scans was poor in 9 instances and there was no correlation between scan activity index and clinical and biological assessment. Correlation between G-111In scans and radioendoscopic data was excellent in 13 instances. Scan activity index was correlated with the Best index and with the intestinal alpha-1-antitrypsine clearance. Faecal excretion (range. 1 - 40%) and daily intestinal granulocytes clearance values (range. 03 - 50 milliards) were only correlated with protein loss parameters. So S-99mTc scan does not appear to be reliable, while intestinal G-111In clearance, not such easy to perform, can give an accurate assessment of IBD activity

A novel zoledronic acid (ZL) derivative, 1-hydroxy-2-(2-ethyl-4-methyl-1H-imidazol-1-yl)ethane-1,1-diyldiphosphonic acid (EMIDP), was prepared and labeled with {sup 99m}Tc successfully in a high labeling yield and good stability in vitro. The preclinical pharmacological properties of {sup 99m}Tc-EMIDP were investigated and compared with {sup 99m}Tc-MDP and {sup 99m}Tc-ZL. The studies of biodistribution in mice and SPECT bone imaging of the rabbit suggest that {sup 99m}Tc-EMIDP has highly selective uptake in the skeletal system and rapid clearance in the soft tissues. The present findings indicate that {sup 99m}Tc-EMIDP holds great potential for bone scintigraphy.

The biological distribution studies of {sup 99m} Tc-ECD in mice were performed in this work. Using ANACOMP computer program, a composed by seven compatiments was adjusted, characterized by a fast blood clearance, an undirectional renal depuration and intestinal elimination, determined by intense hepato biliary transit. Plasma, bile and urinary samples were analysed by HPLC, showing the in vivo metabolism of the compound. (author)

Technetium-99m P.G. cholescintigraphy was performed in 27 human volunteers and 81 patients referred for hepatobiliary tract disease. The gallbladder, biliary system, and gastrointestinal tract were well visualized in the normal patients and volunteers. The gallbladder was not visualized in 22 patients with histologically proved cholecystitis with cystic duct obstruction. Nine patients with complete extrahepatic obstruction of the common bile duct were correctly diagnosed. Hepatocellular disease and incomplete obstruction, with and without jaundice, were diagnosed with this technique. Oral cholecystography is superior to this method for the detection of cholelithiasis in nonjaundiced patients.

Objective: To assess the feasibility of hepatic asialoglycoprotein receptor scintigraphy using 99mTc-lactosylated human serum albumin (LSA), a newly synthesized radiopharmaceutical with convenient labeling method, in the evaluation. of hepatic functional status, in vivo imaging study with LSA was performed in rats with. acute hepatic injury induced by dimethylnitrosamine (DMN). Results were compared with changes in liver enzyme profiles and histological findings. Methods: DMN (27 mg/kg) was injected i.p. in 20 SD rats to induce acute hepatic injury. Dynamic and static imaging of the chest and abdomen were acquired for 30 minutes after i.v. injection of LSA at the 3rd (DMN-3), 8th (DMN-8), and 21st (DMN-21) days after DMN treatment. Time-activity curves of the heart and the liver were generated from anterior images. Degree of hepatic uptake and blood clearance were evaluated with visual interpretation and semiquantitative analysis using receptor index (LHL3) and index of blood clearance (HH3). Time to maximal binding (Tmax) and slope of the curve (K value) were acquired with maximal likelihood curve fitting method using Prism program. Results: Increases in liver enzymes (AST and ALT) and changes in histological findings (centrilobular necrosis and cellular infiltration) were the most prominent in DMN-3 group, and to a lesser extent after then. Hepatic tracer uptake was lower in DMN-treated rat group. In semiquantitative analysis, LHL3 was significantly lower in DMN-treated rat group than in control group (DMN-3: 0.842, DMN-8: 0.898, DMN-21: 0.91, Control: 0.96, p99mTc-LSA liver scintigraphy could be used in initial evaluation of acute hepatic injury and follow-up studies for recovery. (authors)

Bisphosphonates can be labeled with Technetium-99m (99mTc) and are used for bone imaging because of their good localization in the skeleton and rapid clearance from soft tissues. Over the last decades bone scintigraphy has been used extensively in the evaluation of oncological patients to provide information about the sites of bone lesions, their prognosis and the effectiveness of therapy by showing the sequential changes in tracer uptake. Since the lesion visualization and lesion/bone ratio are important utilities for a bone scanning radiopharmaceutic; in this study incorporation of 99mTc labeled alendronate sodium (99mTc-ALD) was evaluated in U2OS (human bone osteosarcoma) and NCI-H209 (human bone carcinoma) cell lines. ALD was directly labeled by 99mTc, radiochemical purity and stability of the complex were analyzed by radioactive thin layer chromatography and radioactive high performance liquid chromatography studies. For cell incorporation study, NCI-H209 and U2OS cell lines were used with standard cell culture methods. The six well plates were used for all experiments and the integrity of each cell monolayer was checked by measuring its transepithelial electrical resistance (TEER) with an epithelial voltammeter. Results confirmed that ALD was successfully radiolabeled with 99mTc. 99mTc-ALD incorporated with NCI-H209 and U2OS cells. The uptake percentages of 99mTc-ALD in NCI-H209 and U2OS cell lines were found significantly different. Since 99mTc-ALD highly uptake in cancer cell line, the results demonstrated that radiolabeled ALD may be a promising agent for bone cancer diagnosis. (author)

Early and reliable diagnosis of colorectal cancer continues to be demanding and challenging. Colorectal cancer cells express Vasoactive Intestinal Peptide (VIP) receptors in high density. We have prepared a VIP analog (TP3654), labeled it with 99mTc, and evaluated it in experimental animals as an agent for imaging colorectal cancer. The tissue distribution of 99mTc-TP3654 has been compared with that of 111In-DTPA-Octreotide and 99mTc-anti-CEA scan in nude mice bearing human colorectal cancer LS174T. Finally, pharmacokinetic and tissue distribution studies of 99mTc-TP3654 have been performed in four normal human volunteers. Data suggest that 99mTc-TP3654 can be prepared efficiently without loss of its receptor specificity and biological activity. Although the 24 hr tumor uptake of 99mTc-TP3654 in the animal model used was modest (0.21 ± 0.07% I.D./g), the tissue distribution profile was more favorable than that of 111In-DTPA-Octreotide or 99mTc-anti-CEA scan. Human studies indicated that 99mTc-TP3654 had no adverse effect in any subject. Within 24 hours, approximately 70% of the injected dose cleared through the kidneys, and approximately 20% through the hepatobiliary system. In these non-fasting volunteers hepatobiliary clearance was slow and in cancer patients tumor uptake was rapid. Data suggest that 99mTc-TP3654 is a promising agent for imaging colorectal cancer

Two cases are presented wherein 99mTc-dextran (99mTc-Dx) imaging localised focal pathology in the small intestine and contributed in reaching a preoperative diagnosis. In the first case, 99mTc-pertechnetate and 99mTc-Dx accumulated in a suspected Meckel's diverticulum equally well. 99mTc-Dx additionally identified exudative discharge from the lesion. In the second case, 99mTc-Dx identified a distal ileal lesion later proved to be a non-specific ulcer on surgery. 99mTc-Dx scanning may have a role in imaging of occult intestinal lesions. (author)

An antitumor agent paclitaxel (PAC) has been proved to be efficient in the treatment of breast and ovarian cancer. Glucuronic acid-derived paclitaxel compound (paclitaxel-glucuronide (PAC-G)) was enzymatically synthesized using microsome preparate separated from rat livers. The biodistribution mechanism of PAC-G in healthy female Albino Wistar rats has been investigated. The expected structure is confirmed according to LC/MS results, and the possible attachment is to C2-hydroxyl group. PAC-G was labeled with {sup 99m}Tc and the radiochemical yield of radiolabeled compound ({sup 99m}Tc-PAC-G) was 98.0 {+-} 02.74% (n=9). The range of the breast/blood and breast/muscle ratios is approximately between 3 and 35 in 240 min. All these experimental studies indicate that {sup 99m}Tc-PAC-G may potentially be used in breast tissue as an imaging agent. (orig.)

Tc-99m is widespread radioisotope in nuclear medicine and it can be produced by two different methods. The first method is performed by chromatographic genera tory by using Mo-99 prepared by fission of U-235, and another method is activation of Mo-99 can be complexed by ZrOCl2 and produce a gel. Mo-99 remains in this gel and Tc-99m elute with normal saline solution. Many factors such as P H, concentration of Mo in the gel structure, and drying conditions of gel affect on the efficiency of the generator. In this research the gel generator production and some factors which are effecting on the 99m Tc production are presented

We have investigated Technetium 99m erythromycin lactobionate (Tc 99m EL) clearance from the lungs after inhalation, in the presence of an alveolitis. Eighteen patients (6 sarcoidosis, 7 idiopathic fibrosis, and 5 miliary tuberculosis) were imaged after the patients inhaled 1,110 MBq of Tc 99m EL. Clearance half time for the first 45 min, for 24 h, and retention at 24 h correlated with percentage of lymphocytes in bronchoalveolar lavage fluid (BAL) (r=.729, r=.883, and r=.826, respectively). There was a positive correlation between peripheral penetration (PP) and forced expiratory volume in 1 s (FEV{sub 1}) (r=.806) and forced vital capacity (FVC) (r=.781). Retention was more marked in sarcoidosis compared with tuberculosis (0.025

99m EL may be related to number of BAL cells or presence of a lymphocytic alveolitis. Long residency time of Tc 99m EL in the lungs implies that erythromycin can also be administered by inhalation for therapeutic purposes.

We have investigated Technetium 99m erythromycin lactobionate (Tc 99m EL) clearance from the lungs after inhalation, in the presence of an alveolitis. Eighteen patients (6 sarcoidosis, 7 idiopathic fibrosis, and 5 miliary tuberculosis) were imaged after the patients inhaled 1,110 MBq of Tc 99m EL. Clearance half time for the first 45 min, for 24 h, and retention at 24 h correlated with percentage of lymphocytes in bronchoalveolar lavage fluid (BAL) (r=.729, r=.883, and r=.826, respectively). There was a positive correlation between peripheral penetration (PP) and forced expiratory volume in 1 s (FEV1) (r=.806) and forced vital capacity (FVC) (r=.781). Retention was more marked in sarcoidosis compared with tuberculosis (0.025< p≤0.05). Radioaerosol lung imaging may reflect the pulmonary function impairment in parenchymal lung diseases. Retention of Tc 99m EL may be related to number of BAL cells or presence of a lymphocytic alveolitis. Long residency time of Tc 99m EL in the lungs implies that erythromycin can also be administered by inhalation for therapeutic purposes

Phase II study of {sup 99m}Tc-DTPA-galactosyl human serum albumin ({sup 99m}Tc-GSA), a new radiopharmaceutical which binds to the asialoglycoprotein receptors on the hepatocytes, was performed in 81 patients with liver diseases to validate its safety and possibility for the evaluation of hepatic function. None of adverse reactions, abnormal clinical laboratory findings and anti-{sup 99m}Tc-GSA antibody production due to {sup 99m}Tc-GSA was recognized. Immediately after the injection of {sup 99m}Tc-GSA, the dynamic data and serial hepatic images were obtained for 60 min. The indices for blood clearance and liver accumulation were calculated based on the counts in the regions of interest on the hearts and livers. In 54 patients with chronic hepatic disorders such as liver cirrhosis, the blood clearance and liver accumulation of {sup 99m}Tc-GSA were retarded according to the progress of the hepatic disorders. The findings of {sup 99m}Tc-GSA scintigraphy also reflected the hepatic functions of the patients with large hepatic tumors, obstructive jaundice and acute hepatitis. These results suggest that {sup 99m}Tc-GSA has the clinical potentials to evaluate the liver functions in the patients with hepatic disorders. (author).

The aim of this study is to assess the accuracy of the pre-existing single-plasma-sample method (SPSM) to measure the glomerular filtration rate (GFR) with Tc-99m-diethylenetriamine pentaacetic acid (Tc-99m-DTPA) in children and adolescents. In addition, the age-independent SPSM is evaluated with two algorithms (Bubeck and Russell) applied for Tc-99m-mercaptoacetyltriglycine (Tc-99m-MAG3) SPSM. The study was performed on 14 patients (12 men and 2 women; age range 3 to 19 yr) with renal diseases. Tc-99m-DTPA (5 MBq/kg) was injected intravenously and thereafter blood samples were taken at 5, 15, 60, 90, 120, 150 and 180 min via the indwelling tube. Radioactivity in the injection syringe and plasma was measured by means of a double-well single-plastic scintillation counter. The true'' GFR as a reference was determined by two methods: 2-exponential curve fitting 7 samples (GFR7) and 1-exponential curve fitting 3 samples between 90 and 150 min (GFR3) in a slow clearance phase. The GFR7 and GFR3 were searched for to the clearance (GFR1) estimated from a plasma concentration at various sample times by means of 3 equations designed for children (Groth and Aasted, Ham-I and -II) and 3 for adults (Christensen and Groth, Jacobsson, Itoh). All the SPSM showed close correlations (r>0.95) with the reference methods. Among them, Jacobsson's equation at sample time=120 min tended to be the most accurate (r=0.9826, root mean squared error (RMSE)=7.8 ml/min)). On the other hand, Ham-I's equation at sample time=120 min was the most accurate, when it was referred to GFR3 in correction for overestimation (r=0.9951, RMSE=4.60 ml/min). The Bubeck and Russells' algorithms showed that the regression equation between the GFR7 and the estimates was different in 2 groups of adults (49 cases) and children/adolescents. Our study indicates that Jacobsson's and Christensen and Groth's equations designed for adults are also applicable in determining the GFR with Tc-99m-DTPA in children and

Three derivatives of N-pyridoxylamino acid were synthesized: /sup 99m/Tc(Sn)-N-pyridoxylphenylalanine, -N-pyridoxyltryptophan, and -N-pyridoxyl-5-methyltryptophan. The chemical and biologic properties of each complex was found to be quite analogous to those of the corresponding /sup 99m/Tc(Sn)pyridoxylideneaminate. In rats, /sup 99m/Tc(Sn)-N-pyridoxyl-5-methyltryptophan [/sup 99m/Tc(Sn)PHMT] showed rapid blood clearance, fast hepatobiliary transit, low urinary excretion, and no intestinal reabsorption. Over 90% of the dose arrived in the intestine through the liver at 30 min after i.v. administration, whereas only 2% of the dose escaped through the kidneys. In rabbits the gallbladder was clearly visualized within 5 min of injection and no renal or bladder images were noted on any scintiphotos. The BSP (sulfobromophthalein) intervention study revealed that the biliary excretion of /sup 99m/Tc(Sn)PHMT is much more resistant than that of /sup 99m/Tc(Sn) diethyl-IDA to the intervention of BSP and hence to serum bilirubin. Toxicity studies on PHMT and Sn-PHMT indicated a wide margin of safety for the proposed human dose

In a search for a fatty acid analogue suitable for labelling with sup(99m)Tc for myocardial imaging, analogues of the general formula X-Y-COOH where the ligand groups X, Y were NH2, SH or COOH, capable of forming complexes with metal ions, were synthesized. Among many such, one compound (CH2(SH).CH2(SH).(CH2)8.COOH) was selected for further study. Injected intravenously together with a reducing agent into mice, rats and one dog, the compound proved unsatisfactory for the purpose because of its toxicity and its failure to localize in the myocardium. The search for alternative analogues and alternative labelling procedures must continue

Full Text Available We quantitatively evaluated total and individual renal function by technetium-99m mercaptoacetyltriglycine (Tc-99m MAG3 renal scintigraphy before and after radiofrequency ablation (RFA of renal tumors. Eleven patients who underwent Tc-99m MAG3 renal scintigraphy 1 week before and after RFA were evaluated (7 men and 4 women ; age range : 23-83 years ; mean age : 60.6 years. Five patients had solitary kidneys, and five had normally or minimally functioning contralateral kidneys. One patient had a renal cell carcinoma in the contralateral kidney. One patient with a solitary kidney underwent RFA a second time for a residual tumor. In patients with a solitary kidney, MAG3 clearance decreased after 5 of 6 RFAs, and in patients with a normally functioning contralateral kidney, MAG3 clearance decreased after 4 of 5 RFAs, but no significant differences were observed between before and after treatments. In addition to the total MAG3 clearance, the split MAG3 clearance was evaluated in patients with a normally functioning contralateral kidney. MAG3 clearance decreased in 4 of 5 treated kidneys, while it adversely increased in the contralateral kidneys after 4 of 5 RFAs. No significant differences, however, were observed between before and after treatments. The results of our study revealed no significant differences in sCr, BUN, CCr, or MAG3 clearance between pre- and post-RFA values. These results support data regarding the functional impact and safety of renal RFA in published reports. We evaluated total and individual renal function quantitatively using Tc-99m MAG3 renal scintigraphy before and after treatment. This scintigraphy was very useful in assessing the effects of RFA on renal function.

Three patients in whom Caroli's disease was diagnosed by cholangiographic methods were studied by scintigraphy with Tc-99m DISIDA. Cholescintigrams showed an intense concentration of the radionuclide in the form of round spots near the hepatic hilus in late images. In two patients with cholestasis, a delayed hepatic clearance of the radionuclide was observed, which improved when the exploration was performed after a choledocoduodenostomy. Tc-99m DISIDA is not only a good noninvasive method to diagnose Caroli's disease, but also a useful technique to evaluate the patency of the biliary tree during the follow-up of such patients

Tc-99m-DTPA-galactosyl-human serum albumin (Tc-99m-GSA) was applied as an agent for receptor-binding hepatic scintigraphy. A single dose of 3-10 mg/185 MBq (5 mCi) Tc-99m-GSA per body was administered in four healthy volunteers and three patients. Time-activity curves for 60 (40) min after injection were obtained from the regions-of-interest over the heart and lung (background). Exponential regression curve was generated from the heart curve during 2-60 (40) min after background subtraction with nonlinear least squares method. Regression curve was well fitted to the heart curve and a significant correlation coefficient of 0.997±0.003 was obtained between these two curves. Absolute dose of GSA in the blood was decided on the assumption that extrapolated value of regression curve at time 0 represented the total injected dose. The absolute dose differences between sample blood and regression curve were 1.4-4.3% (mean). Nonlinear regression analysis is useful for estimating quantitative dose of GSA in blood without any blood samples. (author)

99mTc-N-pyridoxyl-5-methyltryptophan (99mTc-PMT) hepatograms were analyzed to provide information about the liver and bile duct. Calculations were based on a four compartmental model and included corrections for blood, tissue, hepatic parenchymal and bile backgrounds. The time activity curves for 99mTc-PMT in the cardiac region were described as the sum of two exponential functions, while curves for the hepatic regions were described as the sum of three exponential components. The measured hepatograms were compared with simulations and good agreement between the two curves showed that the compartmental model adequately described the blood and bile activities in vivo. Hepatic excretion rate constants were 0.179 ± 0.026 in three normal subjects, 0.102 ± 0.012 in four patients with chronic hepatitis and 0.082 ± 0.034 in six patients with liver cirrhosis. In the case of diffuse parenchymal liver disease, there were lower rate constants for the excretion from the liver to the bile ducts than in normals, and the relative distribution volumes were also larger than normal. Prior to the development of this compartmental model, no useful kinetic model had been found which could satisfactorily explain the time activity curves. Experience in human studies proves this method to be accurate in determining the rate constants for the hepatobiliary transport of 99mTc-PMT. (orig.)

Tc-99m N-pyridoxyl-5 methyltryptophan (Tc-99m PMT) hepatograms were analyzed to provide information about the liver and bile duct. Calculations were based on a 4 compartmental model and included corrections for blood, tissue, liver and bile backgrounds. The time-activity curves for Tc-99m PMT in the cardiac region were described as the sum of 2 exponential functions, while curves for the hepatic region were described as the sum of 3 exponential components. The measured hepatograms were compared with simulated hepatograms and good agreement between the two curves showed that the compartmental model adequately described the blood and bile activities in vivo. Hepatic excretion rates were 0.179 +- 0.028 in 3 normal subjects. 0.102 +- 0.012 in 4 patients of chronic hepatitis and 0.116 +- 0.061 in 6 patients of liver cirrhosis. In the cases of diffuse parenchyal liver diseases, there were lower rate constants for the excretion from the liver to the bile ducts than in normals and the relative distribution values also larger than normal. Prior to the development of this compartmental model, no useful kinetic model had been found which could satisfactorily explain the time-activity curves. Experience in human studies proves this method to be accurate in determining the rate constants for hepatobiliary transport of Tc-99m PMT

This paper describes a modification in the process to obtaining Tc-99m by the extraction method of solvent from Mo-99 produced by irradiation. Tc-99m is considered an ideal radionuclide for medical and biological applications

The bombesin (BN) receptor subtype 2 (GRP-r) is expressed in several normal human tissues and is over-expressed in various human tumors including breast, prostate, small cell lung and pancreatic cancer. Recently [{sup 99m}Tc]EDDA/HYNIC-Lys{sup 3}-bombesin ({sup 99m}Tc-HYNIC-BN) was reported as a radiopharmaceutical with high stability in human serum, specific cell GRP-r binding and rapid cell internalization. The aim of this study was to evaluate the feasibility of using {sup 99m}Tc-HYNIC-BN to image GRP-r and to assess the radiopharmaceutical biokinetics and dosimetry in 4 breast cancer patients and in 7 healthy women. Methods: Whole-body images were acquired at 20, 90, 180 min and 24 h after {sup 99m}Tc-HYNIC-BN administration. Regions of interest (ROIs) were drawn around source organs on each time frame. The same set of ROIs was used for all 11 scans and the cpm of each ROI was converted to activity using the conjugate view counting method. The image sequence was used to extrapolate {sup 99m}Tc-HYNIC-BN time-activity curves in each organ in order to calculate the total number of disintegrations (N) that occurred in the source regions, according with MIRD methodology. N data were the input for the OLINDA/EXM code to calculate internal radiation dose estimates. Results: Images showed a rapid radiopharmaceutical blood clearance with renal excretion as predominant route. {sup 99m}Tc-HYNIC-BN exhibited high in vivo affinity for GRP-r over-expression successfully visualized in cancer mammary glands and well differentiated from the ubiquitous GRP-r expression in normal breast, lungs and airways. There was no statistically significant difference (p > 0.05) in the radiation absorbed doses between cancer patients and healthy women. The average equivalent doses (n=11) for a study using 740 MBq were 24.8 +- 8.8 mSv (kidneys), 7.3 +- 1.8 mSv (lungs), 6.5 +- 4.0 mSv (breast) 2.0 +- 0.3 mSv (pancreas), 1.6 +- 0.3 mSv (liver), 1.2 +- 0.2 mSv (ovaries) and 1.0 +- 0.2 mSv (red

Full text: Octreotide is a synthetic octapeptide analog of somatostatin. Its major effects inhibit the release of pituitary growth hormone and the endocrine secretions of the pancreas, stomach, and intestine. So it is recommended to control symptoms associated with neuroendocrine tumours. In therapy, it is necessary to estimate patient-specific absorbed dose, especially to dose-limiting risk organs and to the tumour tissue. Kinetic analyses need to be carefully planned, meanwhile absorbed fraction are most similar to the subject in question should be chosen. However, the result of dose assessment is not sufficiently accurate or detailed to guide clinical decision-making, and not well correlated with observed effects on patient's organs and tumours. In this study, 99mTc-HTOC is an excellent indicator that displays the distribution of 188Re- HTOC in patient's body. The kinetic information of 99mTc -HTOC in patient's body can be obtained by SPECT in 1,4 h after injection. The activity in patient's tumours and organs can be calculated by lined the time-activity curve. In the study, the data of 86 cases can be collected. Although the basic formula of dose assessment is based on that of the medical internal radiation dose committee (MIRD), the absorbed fractions have been adjusted to be more patient-specific by patient's CT image and other data. It make internal dose of patients more accurate by the method. (author)

{sup 99m}Tc-EDDA/HYNIC-Tyr{sup 3}-octreotide ({sup 99m}Tc-HYNIC-TOC) has shown high in vitro and in vivo stability, rapid background clearance and rapid detection of somatostatin receptor-positive tumors. The aim of this study was to establish a biokinetic model for {sup 99m}Tc-HYNIC-TOC prepared from lyophilized kits, and to evaluate its dosimetry as a tumor imaging agent in patients with histologically confirmed neuroendocrine tumors. Whole-body images from eight patients were acquired at 5, 60, 90, 180 min and 24 h after {sup 99m}Tc-HYNIC-TOC administration obtained from instant freeze-dried kit formulations with radiochemical purities >95%. Regions of interest (ROIs) were drawn around source organs on each time frame. The same set of ROIs was used for all eight scans and the count per minute (cpm) of each ROI was converted to activity using the conjugate view counting method. The image sequence was used to extrapolate {sup 99m}Tc-HYNIC-TOC time-activity curves in each organ, to adjust a biokinetic model using the SAAM software, and to calculate the total number of disintegrations (N) that occurred in the source regions. N data were the input for the OLINDA/EXM code to calculate internal radiation dose estimates. Images showed an average tumor/blood (heart) ratio of 4.3{+-}0.7 in receptor-positive tumors at 1 h. The mean radiation absorbed dose calculated for a study using 740 MBq was 24, 21.5, 5.5 and 1.0 mSv for spleen, kidneys, liver and bone marrow respectively and the effective dose was 4.4 mSv.

The absorbed dose in the kidneys of adult patients has been assessed using the biokinetics of radiopharmaceuticals containing Tc99m (DTPA) / Tc99m (Mag3) or Tc99m (Dmsa).The absorbed dose was calculated using the formalism MIRD and the Cristy-Eckerman representation for the kidneys. The absorbed dose to the kidneys due to Tc99m (DTPA) / Tc99m (Mag3), are given by 0.00466 mGy.MBq-1 / 0.00339 mGy.MBq-1. Approximately 21.2% of the absorbed dose is due to the bladder (content) and the remaining tissue, included in biokinetics of Tc99m (DTPA) / Tc99m (Mag3). The absorbed dose to the kidneys due to Tc99m (Dmsa) is 0.17881 mGy.MBq-1. Here, 1.7% of the absorbed dose is due to the bladder, spleen, liver and the remaining tissue, included in biokinetics of Tc99m (Dmsa). (Author)

Psycho-pharmacology has been discovering much about the D 2 dopamine receptors and their interrelationship to brain pathologies such as Parkinson's Disease, Schizophrenia and Huntington Disease. Those biological receptors have got affinity with dopamine endogenous agent, so that they complex and, in non pathological individuals, the biological receptors contribute to bring the levels of dopamine and free acetylcholine into equilibrium. The D 2 antagonistic psychotropic agents because of having got strong affinity with those receptors, have been being transformed into radiopharmaceuticals to diagnose these pathological disease of Central Nervous System. The Spiperone Dithiocarbamate complex studied by us, is a potential diagnosis agent because of being highly lipo-soluble and having close relationship with D 2 receptors. Besides, it is a photon emitter, allowing the use of SPECT (Single Photon Emission Computed Tomography) technique which is economically less expensive if compared to the PET (Positron Emission Tomography) technique. The Spiperone Dithiocarbamate (SPDC) is synthesized from Spiperone and its complexation with Technetium-99m has been prepared with its reaction parameters after being studied and improved. The SPDC-99m Tc complex biological distribution have made in Wistar rats and the uptake of spleen, heart, liver stomach, lung, kidney, blood, intestine and brain have been resolved. The plasmatic clearancecurve has been based on Wistar rats data and the know-how of the kit (for label SPDC with Tc) has been achieved. (author). 5 figs, 4 tabs

The bombesin (BN) receptor subtype 2 (GRP-r) is expressed in several normal human tissues and is over-expressed in various human tumors including breast, prostate, small cell lung and pancreatic cancer. Recently [99mTc]EDDA/HYNIC-Lys3-bombesin (99mTc-HYNIC-BN) was reported as a radiopharmaceutical with high stability in human serum, specific cell GRP-r binding and rapid cell internalization. The aim of this study was to evaluate the feasibility of using 99mTc-HYNIC-BN to image GRP-r and to assess the radiopharmaceutical biokinetics and dosimetry in 4 breast cancer patients and in 7 healthy women. Methods: Whole-body images were acquired at 20, 90, 180 min and 24 h after 99mTc-HYNIC-BN administration. Regions of interest (ROIs) were drawn around source organs on each time frame. The same set of ROIs was used for all 11 scans and the cpm of each ROI was converted to activity using the conjugate view counting method. The image sequence was used to extrapolate 99mTc-HYNIC-BN time-activity curves in each organ in order to calculate the total number of disintegrations (N) that occurred in the source regions, according with MIRD methodology. N data were the input for the OLINDA/EXM code to calculate internal radiation dose estimates. Results: Images showed a rapid radiopharmaceutical blood clearance with renal excretion as predominant route. 99mTc-HYNIC-BN exhibited high in vivo affinity for GRP-r over-expression successfully visualized in cancer mammary glands and well differentiated from the ubiquitous GRP-r expression in normal breast, lungs and airways. There was no statistically significant difference (p > 0.05) in the radiation absorbed doses between cancer patients and healthy women. The average equivalent doses (n=11) for a study using 740 MBq were 24.8 +- 8.8 mSv (kidneys), 7.3 +- 1.8 mSv (lungs), 6.5 +- 4.0 mSv (breast) 2.0 +- 0.3 mSv (pancreas), 1.6 +- 0.3 mSv (liver), 1.2 +- 0.2 mSv (ovaries) and 1.0 +- 0.2 mSv (red marrow). The mean effective dose was 3

Tc-99m-HMPAO reflects tissue perfusion but Tc-99m-ECD uptake is affected by tissue viability in addition to tissue perfusion which the varied state of cellular retention of Tc-99m-ECD reflects. Luxuriously perfused area on Tc-99m-HMPAO SPECT implies that this cortex was already reperfused either spontaneously or after thrombolysis and that accompanied paralysis of vascular reactivity in those zones warms progressive deterioration. We tried to find out if we can use sequential Tc-99m-ECD/Tc-99m-HMPAO SPECT to reveal cortical perfusion and severity and range of risky areas of cerbral cortex despite reperfusion in sub-acute infarction. In 13 patients (M ; F =7 : 6, mean age 57 (range: 26-84)) with cortical (n=12) and basal ganglia infarction (1), we performed sequential Tc-99m-ECD/Tc-99m-HMPAO SPECT at the same position. At first, 555 MBq of Tc-99m-ECD was injected and imaged and then 1110 MBq of Tc-99m-HMPAO was injected again and imaged with the patients in situ, and the first image (Tc-99m-ECD) and the subtracted image (2nd- 1st : Tc-99m-HMPAO) were compared slice by slice. Study was done from 3 days to 31 days (16{+-}9) after ictus. Tc-99m-ECD uptake was always less than or equal to Tc-99m-HMPAO uptake at the lesion in all cases. Luxury perfusion was prominent in four patients. Mismatched uptake was found in 10 patients. Severity of mismatch showed diverse spectrum and was ranged from total middle cerebral artery territory (1 case) to peripheral thin zones around infarction (2 cases). The other 7 showed intermediate amount of tissues with mismatch , i.e., Tc-99m-ECD defects where Tc-99m-HMPAO uptake is in part increased, normal or decreased. Upon discharge, patients having more uptake with Tc-99m-ECD predicted improvement. Patients having mismatched uptake went dichotomous way. In conclusion, Tc-99m-ECD/Tc-99m-HMPAO sequential SPECT is feasible and reveal both tissue perfusion (Tc-99m-HMPAO ) and discrepant Tc-99m-ECD uptake probably reflecting viability in acute

Tc-99m-HMPAO reflects tissue perfusion but Tc-99m-ECD uptake is affected by tissue viability in addition to tissue perfusion which the varied state of cellular retention of Tc-99m-ECD reflects. Luxuriously perfused area on Tc-99m-HMPAO SPECT implies that this cortex was already reperfused either spontaneously or after thrombolysis and that accompanied paralysis of vascular reactivity in those zones warms progressive deterioration. We tried to find out if we can use sequential Tc-99m-ECD/Tc-99m-HMPAO SPECT to reveal cortical perfusion and severity and range of risky areas of cerbral cortex despite reperfusion in sub-acute infarction. In 13 patients (M ; F =7 : 6, mean age 57 (range: 26-84)) with cortical (n=12) and basal ganglia infarction (1), we performed sequential Tc-99m-ECD/Tc-99m-HMPAO SPECT at the same position. At first, 555 MBq of Tc-99m-ECD was injected and imaged and then 1110 MBq of Tc-99m-HMPAO was injected again and imaged with the patients in situ, and the first image (Tc-99m-ECD) and the subtracted image (2nd- 1st : Tc-99m-HMPAO) were compared slice by slice. Study was done from 3 days to 31 days (16±9) after ictus. Tc-99m-ECD uptake was always less than or equal to Tc-99m-HMPAO uptake at the lesion in all cases. Luxury perfusion was prominent in four patients. Mismatched uptake was found in 10 patients. Severity of mismatch showed diverse spectrum and was ranged from total middle cerebral artery territory (1 case) to peripheral thin zones around infarction (2 cases). The other 7 showed intermediate amount of tissues with mismatch , i.e., Tc-99m-ECD defects where Tc-99m-HMPAO uptake is in part increased, normal or decreased. Upon discharge, patients having more uptake with Tc-99m-ECD predicted improvement. Patients having mismatched uptake went dichotomous way. In conclusion, Tc-99m-ECD/Tc-99m-HMPAO sequential SPECT is feasible and reveal both tissue perfusion (Tc-99m-HMPAO ) and discrepant Tc-99m-ECD uptake probably reflecting viability in acute or

99mTc-galactosyl human serum albumin (99mTc-GSA) is a newly developed receptor-binding agent, specific for the asialoglycoprotein receptor, which resides exclusively on the plasma membrane of mammalian hepatocytes. Liver scintigraphy using 99mTc-GSA was performed on 65 patients with liver diseases. Dynamic data were obtained by gamma camera during 20 minutes after the intravenous injection of 3 mg (185 MBq) of 99mTc-GSA. The maximum removal rate of 99mTc-GSA (denoted as P (2)) was measured by two methods: nonlinear five-compartment model analysis adopting the Michaelis-Menten constant for the transfer of 99mTc-GSA from hepatic blood to receptor, and a graphical plot using compartmental dose curves. The graphical plot could estimate easily the maximum removal rate in terms of two data points of 0 and 1 minutes without nonlinear least squares and numerical integration. The results indicated that the maximum removal rate was decided immediately after the intravenous injection of 99mTc-GSA. Although 99mTc-GSA is recognized to accumulate nonlinearly on the liver, the rate constant P (2)* (1/min) of transfer from hepatic blood to the receptor was estimated by graphical plot, assuming a linear five-compartment model. P (2)* Km, which was given by the product of the rate constant P (2)* and the Michaelis constant Km, was well correlated with P (2). Next, for 99mTc-GSA liver scintigraphy, we applied a Patlak plot that was applicable to the linear system, and the rate constant Ku of transfer from extrahepatic blood to the liver was estimated. From the results of graphical plot, it was theoretically shown that Ku represented P (2). This was confirmed by clinical data. (author)

Liver Scintigraphy using 99mTc-DTPA-galactosyl-human serum albumin is a modern diagnostic tool that can be used to evaluate postoperative liver function in patients with biliary atresia. Calculating the HH15 (Clearance index) and LHL15 (receptor index) indicates the hepatic functional reserve. We evaluated 11 patients with biliary atresia using liver scintigraphy to assess the chronological changes in liver function postoperatively. Results were compared with laboratory data HH15 and LHL15 obtained by liver scintigraphy using 99mTc-GSA improved after portoenterostomy, however, no correlation with laboratory data could be found. Even preoperative results were within the normal range for adults suggesting that the normal range of HH15 and LHL15 in children must differ from the adult range. The present study suggests that 99mTc-GSA scintigraphy will be able to assess the hepatic functional reserve which can not be detected by various other conventional liver function tests. (author)

By using sup(99m)-Tc-d1 DMS labeled with 99m-Tc using stannous chloride and prepared with freeze-dried d1-DMS containing a 3:1 molar ratio of DMS and Sn+2 the effect of stereochemical factor of DMS on kidney affinity, renal images, blood clearance, urinary excretion was studied in experimental animals and two normal volunteers and 75 patients. The comparation revealed a quite similar formation of complex II from d1-DMS to that from the meso-form, judge from its absorption spectra and absorption behavior into the gel. The stereochemical difference of DMS is not a critical factor for the formation of the sup(99m)-Tc-DMS complex with high affinity for the kidney, although it is believed that the renal accumulation of Tc-complex will depend greatly on chemical configuration of the complex. (APR)

The use of radiotracers in research of animal venom has been scarce, although it allows an excellent approach to follow the process of biodistribution and kinetics of toxins, and tissue distribution studies are very important for clinical use. Our group has demonstrated that Scorpaena plumieri venom (SP) possess high antitumoral activity and can be a source of template molecules for the development of antitumoral drugs. The purpose of this study was to radiolabel SP with 99mTc and investigate its biodistribution profile. High labeling yield was obtained and the results suggest that [99mTc]SP can be an useful tool for in vivo studies. The analysis indicated that SP is excreted manly by the kidneys with a slow clearance rate. The significant [99mTc]SP uptake in the heart and lungs may explain, at least partially, the pulmonary edema and effect cardiac observed by the envenoming. (author)

Cyanocobalamin (CNCbl), a kind of vitamin B12 (cobalamin, Cbl), which has a special binding capability to rapid dividing cells and proliferating tissue, especially tumors, has been modified and labeled by 99mTc. The optimal labeling condition was determined, and the biodistribution of 99mTc-DTPA-b-CNCbl both in normal mice and TA2 mice bearing MA891 mammary tumors were studied. 99mTc-DTPA-b-CNCbl showed low uptake and rapid clearance in nontarget tissues, and renal excretion. About 40% of uptake at 1 hour remained in the tumor at 12 hours p.i. The satisfying ratio of T/NT was acquired at 6 hours p.i. (author)

99mTc-hexamethylpropyleneamineoxime (99mTc-HMPAO) is a reagent for scanning cerebral blood flow. We investigated how 99mTc-HMPAO changed in the blood and brain. The 99mTc-HMPAO, which was prepared by adding of 99mTcO4- to HMPAO and Sn(II), consisted of primary and secondary complexes, reduced hydrolyzed 99mTc, and 99mTc-pertechnetate. The percentage of the primary complex in 99mTc-HMPAO decreased with time after preparation. The primary complex converted to the secondary one very rapidly in the presence of plasma. When 99mTc-HMPAO was injected into patients, 99mTc activity was immediately partitioned in the plasma fraction, with approximately 60% in whole blood. In plasma, 99mTc was found to be associated with proteins such as albumin and globulin. 99mTc trapped in red cells was not washed out with either plasma or saline. Biodistribution studies showed that the less lipophilic compounds of 99mTc-HMPAO could not pass through the blood brain barrier (BBB), and therefore did not accumulate in the brain. The results of gel chromatography and equilibrium dialysis indicated that no specific 99mTc binding protein was present in the brain. Considering the instability of 99mTc-HMPAO in vivo, we proposed that the speed at which the primary complex converted to the less lipophilic compounds was important in allowing 99mTc-HMPAO to pass through the BBB and to be fixed in the brain. (orig.)

Dimethylglyoxime (DMG) labelled with [sup 99m]Tc is presented as a renal imaging agent. The behaviour of this complex was analysed at different pH by means of UV spectral data and using DMG-calcium chloride as a reference complex. Biokinetic data were evaluated in two biological models, Sprague-Dawley rats and Didelphis albiventris argentine opossum. Biodistribution in rats demonstrated fast and specific renal excretion. Time-activity values over both kidneys could be quantified for this complex. Renographic studies led to mean time-to maximum values on twelve assays of 2.0 [+-] 0.1 min and a mean relative function of 53.0 [+-] 2.3 and 47.0 [+-] 3.2 for right and left kidneys, respectively. [sup 99m]Tc-DMG showed specificity for the renal excretion pathway and therefore seems to be a very useful radiopharmaceutical for renal function studies. (Author).

Dimethylglyoxime (DMG) labelled with 99mTc is presented as a renal imaging agent. The behaviour of this complex was analysed at different pH by means of UV spectral data and using DMG-calcium chloride as a reference complex. Biokinetic data were evaluated in two biological models, Sprague-Dawley rats and Didelphis albiventris argentine opossum. Biodistribution in rats demonstrated fast and specific renal excretion. Time-activity values over both kidneys could be quantified for this complex. Renographic studies led to mean time-to maximum values on twelve assays of 2.0 ± 0.1 min and a mean relative function of 53.0 ± 2.3 and 47.0 ± 3.2 for right and left kidneys, respectively. 99mTc-DMG showed specificity for the renal excretion pathway and therefore seems to be a very useful radiopharmaceutical for renal function studies. (Author)

Although extensive work has been done on cigarette smoking and its effects on pulmonary function, there are limited number of studies on water-pipe smoking. The effects of water-pipe smoking on health are not widely investigated. The aim of this study was to determine the effects of water-pipe smoking on pulmonary permeability. Technetium-99m DTPA inhalation scintigraphy was performed on 14 water-pipe smoker volunteers (all men, mean age 53.7±9.8) and 11 passive smoker volunteers (1 woman, 10 men, mean age 43.8±12). Clearance half-time (T 1/2) was calculated by placing a monoexponential fit on the time activity curves. Penetration index (PI) of the radioaerosol was also calculated. PI was 0.58±0.14 and 0.50±0.12 for water-pipe smokers (WPS) and passive smokers (PS) respectively. T 1/2 of peripheral lung was 57.3±12.7 and 64.6±13.2 min, central airways was 55.8±23.5 and 80.1±35.2 min for WPS and PS, respectively (p≤0.05). Forced expiratory volume in one second/forced vital capacity (FEV1/FVC)% was 82.1±8.5 (%) and 87.7±6.5 (%) for WPS and PS, respectively (0.025< p≤0.05). We suggest that water-pipe smoking effects pulmonary epithelial permeability more than passive smoking. Increased central mucociliary clearance in water-pipe smoking may be due to preserved humidity of the airway tracts. (author)

Several radiopharmaceuticals (sup(99m)Tc-Fe-ascorbates, sup(99m)Tc-Sn-DTPA, sup(99m)Tc-Sn-ACD-citrate-complex and sup(99m)Tc-Sn-tetracyclin-HAsc-ACD-complex) for renal and tumour scintigraphy were tested in animal experiments. Also tested was sup(99m)Tc-penicillamine for scintigraphic investigations of the gallbladder and the liver. The findings suggest that the different radiopharmaceuticals have different degrees of reliability and exactness, and that some of them should be combined to achieve better diagnostic values. (GSE/AK)

The m of the present study is to clarify the role of Tc99m-HIG and Tc99m-infecton in assessment of patients with pulmonary TB. Thirty-four patients with pulmonary tuberculosis proved by X-ray, bronchial lavage, sputum analysis and culture were included in the study. Tc99m-infecton and Tc99m-HIG were given intravenous in a dose of 740 MBq (20 md) with imaging after 1 and 4 hours. Images were correlated with clinical, radiological and laboratory data. Tc99m-infecton and Tc99m-HIG showed true positive results in 30 and 24 patients and false negative study in 4 and 10 patients, respectively. The sensitivity of Tc99m-infecton was 88% whereas that of Tc99m-HIG was 70%. When eighteen patients were followed up for 8 months after therapy with anti-tuberculous therapy, sixteen of them showed conversion of mycobacterium culture to negative. Tc99m-infecton images were true negative in 12 of them (specificity 75%) while only 8 of them were true negative on Tc99m-HIG study (specificity 50%) and only 6 were true negative on chest X-ray (specificity 37.5%). It can be concluded that Tc99m-infecton is more sensitive than Tc99m-HIG in diagnosis and monitoring response to treatment of pulmonary tuberculosis

Resistance to chemotherapy constitutes a major obstacle to cancer cures. Cellular mechanisms of resistance involve efflux pumps, P-glycoprotein (Pgp), the product of the MDR1 gene and the related membrane glycoprotein, multidrug resistance associated protein 1 (MRP1). Multidrug resistant cell lines overexpressing Pgp are resistant to a structurally and functionally diverse group of chemotherapeutic agents. Many of these drugs tend to be lipophilic and positively charged at neutral pH. This suggested the application of the two lipophilic cationic 99mTc radiopharmaceuticals currently used for myocardial perfusion, 99mTc-MIBI and 99mTc-Tetrofosmin. Efforts were also made to develop specific 99mTc labelled substrates for Pgp based on lipophilic cationic 99mTc complexes. A large number of studies indicated that 99mTc-MIBI, 99mTc-Tetrofosmin and some related 99mTc compounds are substrates for Pgp. However, it remains uncertain whether these 99mTc labelled compounds are substrates for MRP1. Thus, both 99mTc-MIBI and 99mTc-Tetrofosmin would be general probes of transporter mediated multidrug resistance in tumour cells. (author)

Purpose: Tc-99m p-aminohippuric acid (PAH) is a new radiopharmaceutical labeled with Tc-99m in presence of calcium three sodium salt of DTPA by use of Sn(II) - reduction method. Tc-99m PAH is rapidly secreted by the kidneys in a manner consistent with tubular secretion, as confirmed by rat probenecid studies. The present study aimed at evaluating Tc-99m PAH as renal imaging agent. Methods: After bolus injection of radiopharmaceutical in a Wister rat (17 MBq) and in 10 healthy subjects - 2 normal volunteers and 8 potential kidney. donors (111 MBq) dynamic images were acquired for 20 min in three frame groups. In all patients Tc-99m MAG3 and Tc-99m DTPA studies were also performed several days later, in l day intervals to acquire renal studies for comparison. The scintigraphic images and time/activity curves were analyzed. Results: Rat study gave typical three-phase renogram and satisfactory renal functional images with no significant extrarenal background. During Tc-99m PAH scintigraphy in humans rapid disappearance of radiopharmaceutical from the vascular system and high uptake in kidneys followed by its very fast elimination and low residual activity at the end of the study were registered. Anterior whole body images obtained at 40 min and 3 h post injection to evaluate the distribution of 99mTc-PAH within the body showed neither gallbladder nor liver activity. Mean values of the following semi-quantitative parameters were calculated; time to peak (Tmax): 3.65±0.91, time from peak to 50% of peak activity (T1/2): 6.91±2.71, percentage of residual activity in each kidney at the end of the study: 26±2.71 and split renal function: 51.26±3.92. Mean values of Tmax and T1/2 obtained with Tc-99m PAH were significantly lower in comparison with Tc-99m DTPA. Mean values of relative function did not show any significant difference between three tracers. Conclusion: Our preliminary results confirmed good biological characteristics of 99mTc-PAH, indicating its potential

For-Met-Leu-Phe-Lys (For-MLFK), a chemotactic peptide that binds with high affinity to granulocytes and monocytes, was labeled with {sup 99m}Tc using ethylene dicysteine (EC) as the metal chelating system. EC was selected because of the rapid renal excretion of its {sup 99m}Tc-complex and therefore, was expected to enhance the degree of urinary elimination of the peptide-conjugate. {sup 99m}Tc-EC-For-MLFK was prepared using a preformed chelate approach. After incubation of {sup 99m}Tc-EC-For-MLFK with total blood, 68.1% of the labeled peptide was associated with WBC and 86% of this cell-associated activity was bound to granulocytes. Biodistribution studies in normal mice revealed a very fast blood clearance (4.1% and 0.6% of I.D. in blood at respectively 5 and 60 min p.i.). However, elimination of the labeled peptide proceeds mainly via the hepatobiliary system (24.5% of I.D. in liver and 48.8% of I.D. in intestines at 60 min p.i.) and to a much lower degree via the kidneys (17.9% in renal system at 60 min p.i.). From these results, it is concluded that {sup 99m}Tc-EC-For-MLFK is not suited to image infections, despite its high binding to granulocytes, since it leads to high, non-specific, abdominal activity.

Aim: To investigate in-vitro the uptake and washout of Tc-99m-MIBI and Tc-99m-tetrofosmin in human breast adenocarcinoma and soft tissue sarcoma cell lines. Methods: The uptake of Tc-99m-MIBI and Tc-99m-tetrofosmin (at 370C, 10, 30 and 60 minutes after incubation with 7.4x10E5 Bq each tracer) was investigated in breast adenocarcinoma MCF-7 and SK-BR-3 cells, synovial sarcoma SW 982 cells and chondrosarcoma SW 1353 cells (concentration of 1x10E6 cells/ml incubation medium). Tracer uptake in cells incubated with ouabain (Na/K-ATPase pump inhibitor; 100 μM and 1mM; 15 and 30 minutes), nigericin (increases mitochondrial potential and disrupts cell membrane potential; 5 and 50 μg/ml; 15 minutes) and carbonyl cyanide m-chlorophenylhydrazone (CCCP) (depolarizes mitochondrial membrane; 10 and 100 μM; 30 minutes) was compared to that in cells without incubation with chemical agents (control cells). The washout (at 370C, 10-60 minutes, 30 and 60 minutes after tracer incubation) of Tc-99m-MIBI and Tc-99m-tetrofosmin was studied in MCF-7 cells, SK-BR-3 cells , SW 1353 cells and fibrosarcoma SW 684 cells. Results: Cellular tracer uptake decreased with ouabain (decrease of Tc-99m-tetrofosmin > Tc-99m-MIBI in SK-BR-3 cells and SW 982 cells) and increased with nigericin (increase of Tc-99m-MIBI > Tc-99m-tetrofosmin in all cells) as compared to the uptake in control cells. With CCCP, decrease of Tc-99m-MIBI uptake in cells preincubated with nigericin was higher than that in cells under basal conditions, whereas a similar decrease of Tc-99m-tetrofosmin uptake in these two group of cells was found. Washout of Tc-99m-MIBI from all cells was lower than that of Tc-99m-tetrofosmin. No significant difference in cell-associated activity of both tracers was found between washout after 30 minutes and that after 60 minutes of incubation, in all cells. Washout of Tc-99m-MIBI from SK-BR-3 cells Tc-99m-tetrofosmin) and Na/K-ATPase pump (Tc-99m-tetrofosmin > Tc-99m-MIBI). Tc-99m-MIBI and Tc-99

Kinetics of plasmatic disappearance of 99mTc-heparin and low molecular weight heparin (LMWH) fractions CY 216 and CY 222 were compared in 2 women and 8 men (aged 50-71) with uncomplicated myocardial infarction. The three technetiated heparins were consecutively injected intravenously (67 nanomoles) to each of 10 patients, at intervals of 3-5 days, 14-28 days after acute cardiac onset. The plasma radioactivity was counted in blood samples collected within a period of 5 h. 99mTc-heparin and LMWH fractions CY 216, CY 222 disappeared from plasma following a biexponential clearancecurve with a fast and slow component reflecting the biodistribution (α) and elimination (β) phase. The bioavailability values as well as distribution and elimination rates were similar for all three technetiated heparins. The bulk of injected 99mTc-heparin or LMWH fraction was rapidly distributed to the tissue compartment, whereas the radiocomplex remaining in the circulation was slowly eliminated with a half-time of an average 320 min. Radioactivity eliminated from plasma was only partially (30-50%) excreted in the urine. The results indicate that after a low-dose intravenous administration LMWH fractions CY 216 and CY 222 maintain the pharmacokinetic properties of standard heparin, especially the rapid distribution to the tissue compartment. (author)

The biological distribution studies of 99m Tc-ECD in mice were performed in this work. Using ANACOMP computer program, a composed by seven compatiments was adjusted, characterized by a fast blood clearance, an undirectional renal depuration and intestinal elimination, determined by intense hepato biliary transit. Plasma, bile and urinary samples were analysed by HPLC, showing the in vivo metabolism of the compound. (author)

Tc-99m MIBI (methoxy isobutyl isonitrile) is newly introduced cationic myocardial perfusion agent. For its favorable dosimetry, upto 30 mCi of Tc-99m MIBI can be used in a patient. Therefore, unlike T1-201, first-pass ejection fraction, ventricular wall motion, and SPECT studies are readily evaluated using Tc-99m MIBI on patients who are undergoing myocardial perfusion study. Nineteen individuals entered into this study and 9 of 19 had T1-201 myocardial scintiscan. For the detection of myocardial ischemia, an IV dipyridamole with hand-grip or bicycle exercise was used. Tc-99m MIBI scintigraphic findings are compared to patients 'EKG' T1-201 scans and coronary angiograms. The result were summerized as follows; 1. In 9 cases, Tc-99m MIBI studies were comparable to T1-201 scintiscans. 2. In the remaining 10 cases, Tc-99m MIBI images were correlated well with clinical pictures, EKG, and angiographic findings. 3. Using Tc-99m MIBI, one can easily obtain fist-pass ejection fraction, ventricular wall motion and SPECT studies. It was concluded that Tc-99m MIBI seems to be an excellent agent for myocardial perfusion study. Tc-99m MIBI images are superior in quality than T1-201 images mainly due to high photon yield and ideal energy of Tc-99m MIBI

Objective:To standardize a method and determine normal values for absolute renal uptake of 99m Tc-DMSA in children with normal creatinine clearance. Materials and methods: Twenty-two children (between 7 months and 10 years of age; mean 4.5 years) without clinical evidence of renal disease were studied using 99m Tc-DMSA scintigraphy. Eighteen had normal renal ultrasonography, micturating urethrocystography, creatinine clearance and visual interpretation of the scintigraphy with 99m Tc-DMSA. Four children were excluded, one with incomplete creatinine clearance and three due to reduction in the creatinine clearance. Absolute renal uptake of 99m Tc-DMSA (DMSA-Abs) was expressed as the fraction of the administered dose retained by each kidney six hours after administration of the radiopharmaceutical. Results: DMSA-Abs was 21.8 +- 3.2% for the right kidney and 23.1 +-3.3% for the left kidney. There was no correlation between renal uptake and the age groups studied, although there was a tendency to an increase in the creatinine clearance with age. Conclusion: Normal values of DMSA-Abs can be used as an additional parameter for the initial diagnostic evaluation and during follow-up of renal diseases, mainly when bilateral impairment of renal function is suspected or in a patient with a single functioning kidney (in which renal differential function is of limited value). (author)

(99m)Tc-dimercaptosuccinic acid [DMSA(III)] and colloidal human serum albumin ((99m)Tc-nanocolloid) are widely used radiopharmaceuticals. Recently, in our institution we encountered image quality problems in DMSA scans after changing the brand of syringes we were using, which triggered us to look into the adsorption properties of syringes from different brands for (99m)Tc-DMSA(III) and (99m)Tc-nanocolloid. We also describe a clinical case in which adsorption of (99m)Tc-DMSA(III) caused inferior imaging quality. DMSA and nanocolloid were labeled with (99m)Tc following manufacturer guidelines. After synthesis, syringes with (99m)Tc-DMSA(III) and (99m)Tc-nanocolloid were stored for 15, 30, 60, and 120 min. We evaluated Luer Lock syringes manufactured by different brands such as Artsana, Henke-Sass-Wolf, B. Braun Medical N.V., CODAN Medizinische Geräte GmbH & Co KG, Becton Dickinson and Company, and Terumo Europe. Adsorption of (99m)Tc-DMSA(III) and (99m)Tc-nanocolloid was acceptably low for all syringes (brands with (99m)Tc-DMSA(III) adsorption rates of 36 and 30%, respectively, and for one brand with a (99m)Tc-nanocolloid adsorption rate of 27%. Adsorption of (99m)Tc-DMSA(III) and (99m)Tc-nanocolloid reaches critical levels in syringes produced by two brands, potentially causing poor image quality--for example, in DMSA scans using pediatric radiopharmaceutical doses. It is advised to check the compatibility of any radiopharmaceutical with syringes as an integral part of the quality assurance program. PMID:24569706

The percent renal uptake of Tc-99m DTPA, within 2 to 3 minutes following the radionuclide appearance into the kidneys according to the method by Gates, was correlated well with the sodium thiosulfate clearance determination (n = 75, r = 0.846) as well as the 24-hour creatinine clearance determination (n = 47, r = 0.893). Therefore, the formula for calculation of glomerular filtration rate (GFR) was derived from the linear regression analysis between renal uptake of Tc-99m DTPA and sodium thiosulfate clearance determination, accordingly: GFR (ml/min.) = 8.775 x (% total renal uptake) + 9.685. In the 31 patients without nephrouropathy, the split GFR of left kidney was 53.6 +- 10.9 ml/min. and that of right kidney was 52.0 +- 11.1 ml/min. The radionuclide computed GFR was also examined for the evaluation of split function of renal parenchyma, in comparison with Tc-99m DTPA renogram pattern. In most cases with standard renogram pattern, the split GFR showed the values over 35 ml/min. Most cases with hypofunctioning renogram pattern showed the values of split GFR within the range of 20-35 ml/min. And most cases with nonfunctioning renogram pattern showed the values under 20 ml/min. In the present study, the split GFR determination was found to be a useful and reliable method for the quantitative evaluation of split function of renal parenchyma. (author)

It is extremely important to have a good grasp of the acceptable limit of hepatectomy before operation because postoperative liver failure can take a fatal course; however, baseline data on the limit of hepatectomy have not been clearly defined. We therefore evaluated and compared the predicted remnant liver function obtained by computed tomography(CT) and technetium-99m diethylenetriamine penta-acetic acid-galactosyl human serum albumin (99mTc-GSA) liver scintigraphy in order to obtain precise data regarding remnant liver function before hepatectomy. We investigated 20 patients undergoing hepatectomy using the clearance rate of indocyanine green (KICG) as a parameter, and compared the predicted postoperative KICG obtained by CT and by transaxial single-photon emission tomographic (SPET) images acquired by 99mTc GSA liver scintigraphy before hepatectomy. In GSA studies, based on time-activity curves for the heart and liver, we compared HH15 (heart activity at 15 min divided by heart activity at 3 min), LHL15 (liver activcity at 15 min divided by heart plus liver activity at 15 min) and KL (obtained from the time-activity curve for the liver) in 103 patients. In 58 patients without increased serum bilirubin, KL was compared with KICG. In four patients, occlusion of the right portal vein was performed with the aim of carrying out secondary hepatectomy, and changes in liver volume were compared between CT and 99mTc GSA liver scintigraphy. The correlation coefficient between the postoperative KICG predicted by CT and the actual postoperative KICG was rather poor, at r = 0.569 (P99mTc GSA liver scintigraphy and the actual postoperative KICG was good, at r = 0.788 (PL and HH15 and between KL and LHL15 in 103 patients were very good or good, at r = 0.906 (PL and KICG in 58 patients was very good, at r = 0.916 (P99mTc GSA liver scintigraphy is useful for predicting remnant liver function before hepatectomy and for evaluating changes in regional liver function after

The purpose of this study was to evaluate the use of an external counting technique to provide daily monitoring of kidney transplant function by measuring the renal clearance of Tc-99m(Sn)DTPA. During the first few weeks following transplant, 15 patients had their renal clearance of Tc-99m DTPA measured daily over periods of 5-24 hr. Clearance rates were compared with daily plasma creatinine levels, and the effects of diurnal variation, drug treatment, and physical activity noted. The results show that any significant fall in clearance rate of chelate, indicating a rejection episode, preceded a rise in plasma creatinine levels by at least 24 hr. One episode of transplant failure presented as a sudden deterioration in clearance rate of chelate; in the others the change was more gradual but was still apparent within hours. It is considered that this noninvasive, low-dose, easy-to-perform technique is of considerable value in extended daily monitoring of renal function and is superior to standard daily or twice-weekly renography for the early detection of transplant rejection

.91, respectively) but a weak positive predictive value (0.44 and 0.39, respectively). Nevertheless, Kaplan-Meier curves generated between scintigraphic findings and time free from disease relapse were statistically different only for {sup 99m}Tc-IL2 scintigraphy (log-rank test, P=0.013). These results indicate that {sup 99m}Tc-IL2 scintigraphy can be useful in selecting CD patients in clinical remission who could benefit from preventive therapy to avoid disease relapse. (orig.)

Hepatic transfer function was obtained by deconvolution analysis using dynamic SPECT data of 99mTc-N-pyridoxyl-5-methyl-tryptophan. Minimum, mean and maximum transit times were evaluated from transfer function. Total and regional effective hepatic blood flow (EHBF) was estimated from the uptake constant with single blood sampling. Functional images of minimum, mean and maximum transit times and regional EHBF were constructed. In 12 cases of liver cirrhosis and 8 cases of normal controls, it was shown that there is a good correlation between the total EHBF obtained by the uptake constant and that measured by blood clearance (r=0.96). In cases of liver cirrhosis, averaged total EHBF was markedly decreased (645±162 ml, mean±SD, p<0.001) and averaged mean transit time was significantly prolonged (23.7±3.9 min, p<0.05) as compared with those in normal controls (1382±232 ml, 20.1±2.2 min, respectively). Total EHBF and regional EHBF negatively correlated with the mean transit time (r=-0.52, r=-0.70, respectively). There were a few cases with liver cirrhosis which showed normal transit time and regional EHBF despite marked liver atrophy and decreased total EHBF. This method is thought to be highly valuable in evaluating regional and total liver functions and pathophysiology of diffuse liver diseases. (author)

Objective:To standardize a method and determine normal values for absolute renal uptake of 99m Tc-DMSA in children with normal creatinine clearance. Materials and methods: Twenty-two children (between 7 months and 10 years of age; mean 4.5 years) without clinical evidence of renal disease were studied using 99m Tc-DMSA scintigraphy. Eighteen had normal renal ultrasonography, micturating urethrocystography, creatinine clearance and visual interpretation of the scintigraphy with 99m Tc-DMSA. Four children were excluded, one with incomplete creatinine clearance and three due to reduction in the creatinine clearance. Absolute renal uptake of 99m Tc-DMSA (DMSA-Abs) was expressed as the fraction of the administered dose retained by each kidney six hours after administration of the radiopharmaceutical. Results: DMSA-Abs was 21.8 +- 3.2% for the right kidney and 23.1 +-3.3% for the left kidney. There was no correlation between renal uptake and the age groups studied, although there was a tendency to an increase in the creatinine clearance with age. Conclusion: Normal values of DMSA-Abs can be used as an additional parameter for the initial diagnostic evaluation and during follow-up of renal diseases, mainly when bilateral impairment of renal function is suspected or in a patient with a single functioning kidney (in which renal differential function is of limited value). (author)

The applications of sup(99m)Tc in nuclear medicine are discussed, such as sodium pertechnetate in thyroid and brain scintigraphy, complex compounds in lungs and liver diao.nosis. Technetium generators are classified according to the method of separating sup(99m)Tc from 99Mo. Adsorption generators are used, molybdate-99 is adsorbed on an Al2O3-packed column while pertechnetate-99m is eluted with 0.9% NaCl solution. Also used is continuous pertechnetate-99m extraction with methyl ethyl ketone from 0.5 M potassium molybdate and 2.5 M of potassium carbonate. The manufacture is described of kits for sup(99m)Tc radiopharmaceuticals preparation, eg., Diagos I, a gluconate complex, a lyophilisate for sup(99m)Tc-sodium pyrophosphate injections, a diagnostic kit for lung scintiscanning. (H.S.)

Melphalan is an alkylating agent widely used in the treatment of neoplastic diseases. However, being an α-amino acid it cannot be labeled with Tc-99m by the use of SnCl2 for pertechnetate reduction. The N-carboxy methyl - derivative of melphalan was obtained and its complexing by technetium-99m was examined. A procedure for labelling of melphalan derivative with Tc-99m has been developed. (author). 18 refs, 8 figs, 8 tabs

Using the method of dynamic scintigraphy of the kidneys with a new radiopharmaceutical preparation, 99mTc-mercaptoacetyltriglycine. 35 children with various urological and nephrological diseases were examined. In indicated cases the examination was supplemented with administration of a diuretic, with further projections or indirect mictional cystography. The standard parameters of functional curves and their standard extent were assessed in a group of 18 healthy kidneys. No significant difference was found as compared with results obtained using 131I-hippuran. The assessed values of global clearance attained 66% of the 131I-hippuran clearance values. In 60% of the patients the visualization of the parenchyma and in 80% the visualization of the efferent urinary pathways was better than when 99mTc-DTPA was used. In all instances the scintigrams were better than when 131I-hippuran was used. The new radiopharmaceutical combines the advantages of technetium-labelled preparations and the favorable pharmacokinetic properties of hippuran. It is suitable for quantification of tubular secretion. It is superior to hitherto used substances as regards the quality of visualization and in particular the lower radiation load. Therefore it is especially suited for pediatric practice. (author). 2 tabs., 4 figs., 13 refs

Tc-99m infecton (ciprofloxacin) was introduced recently as an infection imaging agent which is specific for bacteria. If successful, this may prove superior to labelled leucocyte imaging, antibodies and other nonspecific agents in terms of logistics, cost and efficacy. We had recently acquired few kits for Tc-99m infecton preparation. Our preliminary experience suggests that it has high specificity for the infected bone and may be useful in bone tuberculosis. Three cases are presented where both Tc-99m MDP scanning and Tc-99m infecton study were undertaken to highlight the potential of this new agent. (author)

Preparation of 99mTc-ciprofloxacin for diagnosis of bacterial infection was investigated by varying factors which affected this compound. The optimum conditions for preparation of 99mTc-ciprofloxacin and a lyophilized kit for Tc-99m labelling were studied. The results from biodistribution study showed that the percentages of the injected dose per gram tissues of infected area at 1 and 3 hours after injection were around 0.25-0.56. 99mTc-ciprofloxacin was found sterile, pyrogen-free and non-toxic. Radiochemical purity was greater than 90% with greater than 6 hours of stability.

Liver scintigraphy was performed using a newly developed radiopharmaceutical, 99mTc-DTPA-galactosyl-human serum albumin (99mTc-GSA), in 17 patients after hepatic portenterostomy for biliary atresia (age: 3 months-14 years old, body weight: 5.8-39 kg). These patients were divided into two groups; good hepatic function group was 3 cases which had no symptom after operation, and poor hepatic function group was 14 cases which needed some therapeutic procedures for ascending cholangitis, GI tract bleeding etc. Dynamic data were obtained by a gamma camera during 20 minutes after intravenous injection of 1.5-3.0 mg (92.5-185 MBq) of 99mTc-GSA. The livers were clearly delineated in all cases. We calculated HH15 (clearance index) for the index of clearance and LHL15 (receptor index) for the index of hepatic uptake. In good hepatic function group, HH15 was 0.396±0.059 (mean±S.D.), LHL15 was 0.960±0.009. In poor hepatic function group, HH15 was 0.629±0.080, LHL15 was 0.875±0.060. The difference between the mean value of both indices was statistically significant. Using single photon emission CT, inhomogenisity of liver accumulation of 99mTc-GSA was clarified, and focal hepatocyte damage, which could not be detected on CT, was able to be estimated. We consider that 99mTc-GSA liver scintigraphy is a useful study for continuous observation of the patients with biliary atresia. (author)

Radiolabeled antibiotics have been used in nuclear medicine for the diagnosis of bacterial infection. They are used as specific infection-imaging agents because of their affinity to bind with bacteria. Tc-99m Ciprofloxacin is the most widely used infection-imaging agent. The aim of the present work is to increase the shelf life of an in house developed single vial kit for the preparation of Tc-99m Ciprofloxacin. Different methods were used to make the Ciprofloxacin kits. Kits were stored at a temperature of 4 deg. C under nitrogen atmosphere and evaluated for stability by serially estimating the labeling efficiency using instant thin layer chromatography (ITLC) following reconstitution with Tc99m pertechnetate at regular intervals of time up to 90 days after their preparation. The data were subjected to Sigmaplotsoftware version 8.0 for shelf-life analysis. The kits were further evaluated for a number of standard quality control parameters. Kits containing sodium chloride-Ciprofloxacin pellets were found to have a shelf life of 7 months and constantly maintaining a labeling efficiency of 95% Tc-99m Ciprofloxacin. Biodistribution studies in balb/c mice showed significant levels in kidney, liver and intestine. Blood clearance studies showed a slow and biphasic clearance in rabbits. Gamma camera imaging of the rabbits bearing S.aureus infectious lesion confirmed the utility and specificity of the reconstituted kit in imaging infection. The final kit, which was recommended for clinical use was found to be stable for nine months with all its characteristics remaining unchanged from those of the freshly prepared Tc-99m Ciprofloxacin during the entire period of observation. (author)

The scintigram using 99mTechnetium-DTPA galactosyl human serum albumin (99mTc-GSA) which binds to asialoglycoprotein receptors on hepatocytes is a good index of hepatocyte function in various liver diseases in adult patients. In 43 patients (4 months to 30 years old) who had undergone Kasai procedure, we performed 53 series of 99mTc-GSA scintigrams and checked the laboratory data of blood draw and the clinical status. The indices for blood clearance and liver accumulation were evaluated on the basis of the dynamic data after 99mTc-GSA injection. HH15 as an index of the blood clearance, and LHL15 as an index of the accumulation of the hepatocytes were calculated and the HH15/LHL15 ratio (H/L15) was examined. 99mTc-GSA scintigram correlated with liver function and clinical status. Our results revealed that: The deterioration of the liver functions and clinical status correlates proportionally with H/L15. The results of 99m Technetium-GSA scintigram correlate with several liver function tests, especially direct bilirubin, albumin and choline esterase. This scintigram is an useful index of clinical status and hepatic function as well as the change of the hepatic parenchymal reserve in BA patients, especially for the evaluation of liver transplantation. (author)

Pulmonary A-V fistula was diagnosed and classified morphologically based on the pattern of time-activity curves by sup(99m)Tc MAA. If the diameter of the fistula is large, macro-albumin easily reveals a shunt. If the fistula has the form of an ''aneurysm,'' the degree of shunt is generally slight. (author)

By simply incubating Herceptin (trastuzumab) with [{sup 99m}Tc(CO){sub 3}(OH{sub 2}){sub 3}]{sup +} ion in saline, a significant yield of {sup 99m}Tc-labeled trastuzumab was found to be achievable. The effective labeling may be based on that trastuzumab is inherent with endogenous histidine group to which {sup 99m}Tc(I) tricarbonyl ion can be strongly bound. For practical {sup 99m}Tc labeling processing, trastuzumab was purified beforehand from the commercial product, Herceptin (Genentech) via size exclusion chromatography to remove the excipient, {alpha}-histidine and a high-labeled yield could be obtained by incubating the purified trastuzumab with [{sup 99m}Tc(CO){sub 3}(OH{sub 2}){sub 3}]{sup +}. Retention of bioactivity of the {sup 99m}Tc(I)-labeled trastuzumab was validated using a cell binding test.

By simply incubating Herceptin (trastuzumab) with [99mTc(CO)3(OH2)3]+ ion in saline, a significant yield of 99mTc-labeled trastuzumab was found to be achievable. The effective labeling may be based on that trastuzumab is inherent with endogenous histidine group to which 99mTc(I) tricarbonyl ion can be strongly bound. For practical 99mTc labeling processing, trastuzumab was purified beforehand from the commercial product, Herceptin (Genentech) via size exclusion chromatography to remove the excipient, α-histidine and a high-labeled yield could be obtained by incubating the purified trastuzumab with [99mTc(CO)3(OH2)3]+. Retention of bioactivity of the 99mTc(I)-labeled trastuzumab was validated using a cell binding test

99mTc-DMSA (dimercaptosuccinic acid) is known to be a safe and effective agent for static renal imaging. However, it has a long uptake time which is a limiting factor in diagnostic procedures and also leads to a relatively high radiation dose being administered to patients. There is a constant search for possible new renal imaging agents with a good resolution, kidney/liver contrast and low radiation dose to all organs. A series of biguanide derivatives (potential as non-insulin-dependent diabetes mellitus agents) labelled with 99mTc were investigated as potential alternative kidney-imaging agents on theoretical grounds (in silico) and their biodistribution (in vivo) verified in a limited number of animal experiments. Such a dual approach has the benefit that it reduces the number of animal experiments needed to evaluate a potential radiopharmaceutical. The blood plasma model shows little or no complexation of the biguanide type ligands by the metal ions in blood plasma. It was therefore expected that these ligands will clear rapidly through the kidneys and liver (increased lipophilicity). These predictions were verified by studies on single vervets comparing them with 99mTc-DMSA as gold standard. All the biguanide derivatives labelled with 99mTc show liver, kidney and gallbladder uptake in vervets. It was shown that the agent 99mTc-CBIG (carboxylbiguanide) has a very fast kidney clearance, which will reduce the dose to organs (as experienced for 99mTc-DMSA), although it's potential as a kidney agent is limited by its gallbladder uptake. (author)

Objective: To investigate the pharmacological characteristics of 99mTc-TRODAT-1 as an imaging agent for dopamine transporter. Methods: (1) The quality control of one-vial formulation produced in China. (2) Biodistribution in rats. (3) Imaging in normal and hemi-Parkinsonian model monkeys. Results: (1) The radiochemical purity of [99mTc]TRODAT-1 was about 79.9% evaluated by TLC. It was stable for 2.5 hours at room temperature. (2) The clearance of [99mTc]TRODAT-1 in the blood of rats was fast. The major portion of radioactivity was excreted by hepatobiliary system. (3) The brain uptake was moderate. But the agent had high-affinity binding to DAT which was highly concentrated in striatal area and there was no specific uptake in cerebellum. The ratio of ST/CB was high. (4) Pretreatment with haloperidol, a non-competing ligand, did not result in any significant change in the level of striatal uptake. (5) The distribution pattern as well as the brain regional uptake of [99mTc]TRODAT-1 did not display any significant difference between male and female rats at 60 min post-injection. (6) Monkeys' SPECT images clearly displayed the normal uptake and the pathologic changes in striatal area at 3 hours post-injection. The semi-quantitative analysis, ST/CB ratio, could reveal the specific uptake value for [99mTc]TRODAT-1 in reflecting the numeral and functional changes in DAT. Conclusion: [99mTc]TRODAT-1 labeled by one-vial formulation of China can be the imaging agent of DAT in clinical study. It proves to be effective and promising radiopharmaceuticals in vivo assessment of the loss of dopamine neurons in Parkinson's disease and other neurodegenerative disease

99mTc-MAG3 is a standard radiotracer for renal dynamic functional study. Despite its"nproperties for clinical uses, it has numerous technical limitations. 99mTc-EC is also a tubular"nradiotracer for renal imaging, which has not been used worldwide. In this study, the use of 99mTc-EC"nand 99mTc-MAG3 for renal functional study were compared."nMethods: Thirty five patients (20 male, 15 female; mean age of 34.63 ±10.69 years) were entered in"nthe study. About 1...

We investigated the effects of fenoterol, a selective β2 adrenoceptor stimulant, on mucociliary clearance in 12 patients with chronic bronchitis. Mucociliary clearance was measured with a scintillation camera after inhalation of a 99mTc labeled aerosol. Fenoterol was administered one h after acquisition commenced and imaging was maintained for a further two h. Three regions of interest (ROI) were selected over each lung to generate time activity curves. Corrections for decay, alveolar deposition (using 24 h image), cough and movement of activity through each ROI were carried out. An exponential function was fitted to the clearancecurves to determine clearance rates. The increase in percentage clearance after fenoterol administration for the left and right whole lung ROI was 35% and 36% per h respectively (P = 0.006 and 0.020). Fenoterol enhances cilial clearance in chronic bronchitis patients. (orig.)

The 99mTc-MDP kit was prepared by using aseptic technique. The composition of MDP invivo kit including 5 mg MDP, 0.5 mg stannous chloride, 0.5 mg ascorbic acid and 5 mg sodium chloride. The kit produces 99mTc-MDP with more than 95% labelling efficiency at pH 6-7 when mixed with requisite amount of 99mTc-pertechnetate. The preparation has been found sterity, pyrogen free, to be sufficiency stable invitro as well as invivo, blood clearance. After intravenous administrations abound 50% of the dose is accumulated and retained by the skeleton. The kit provides quality product in high yield, more stable than other phosphonate kit, high bone uptake. High avidity of 99mTc-MDP for bone imaging makes it a promising agent for the detection of bone diseases. (author)

Porphyrin-lipid nanovesicles (PLN) have been developed with intrinsic capabilities as activatable multimodal photonic contrast agents. Radiolabeling of PLN encapsulating drugs could eventually be able to provide quantitative in vivo information for diagnosing and treating diseases. In this study, we developed (99m)Tc-labeled porphyrin-lipid nanovesicles ((99m)Tc-PLN) as a cargo-encapsulated formulation without significant impact on liposome integrity and encapsulation stability. 50 mM calcein was encapsulated into PLN by probe sonication. The size of the PLN was about 150 nm. The PLN were then reacted with (99m)Tc using SnCl2 dissolved in 1 mM HCl as a reducing agent and incubated for 10 min at 22 °C. The radiolabeling efficiency and stability of (99m)Tc-PLN were evaluated by instant thin-layer chromatography and low-pressure liquid chromatography (LPLC). (99m)Tc labeling was successful with a >92% labeling efficiency. LPLC showed that the liposomal elution peaks of the porphyrin-lipid and the calcein overlapped with the radioactivity elution peak of (99m)Tc-labeled PLN. The (99m)Tc-labeling procedure did not change the size of PLN. Encapsulated calcein remained inert inside PLN. Thus, this work lays out a simple and effective radiolabeling method using SnCl2 in HCl in the preparation of (99m)Tc-PLN. PMID:24963601

Gel chromatography column scanning (GCS) is a new method for radiochemical quality control. GCS techniques for Technetium-99m radiopharmaceuticals in nuclear medicine have been developed for use in both research and routine clinical work. The dependence on several of the parameters of the GCS method have been investigated, e.g. type of gel, column dimensions, eluent, equilibration, elution volume, flow rate and resolution of the recording system (radiochromatographic scanner or scintillation camera). The GCS method has been compared with conventional gel filtration, thinlayer cromatography (TLC) and paper cromatography (PC). The GCS method is to be preferred due to few artifacts, much information, good reproducibility, rapidity, simplicity and the convenience of the test. The GCS method has been applied to the development of labelling techniques for the new radiopharmaceuticals Tc-99m plasmin and Tc-99m unithiol (2.3 dimercaptopropane sodiumsulphonate), use for investigating deep vein thrombosis and renal cortical morphology respectively. The GCS method has also been applied for studying some labelling parameters, the radiochemical purity and the labelling of Tc-99m macroaggregated albumin, Tc-99m pyrophosphate, Tc-99m methylenedisphosphate, in addition to Tc-99m plasmin and Tc-99m unithiol. (Author)

99mTc-galactosyl human serum albumin (99mTc-GSA) is a newly developed receptor-binding agent specific for the asialoglycoprotein receptor, which resides exclusively on the plasma membrane of mammalian hepatocytes. Liver scintigraphy using 99mTc-GSA was performed on 13 patients with liver disease. Dynamic data were obtained by gamma camera during 40 min after the intravenous injection of 3 mg (185 MBq) of 99mTc-GSA. Heart and liver time activity curves with acquisition times of 40, 30 and 20 min were created, and two different compartment analyses were examined. One was a nonlinear five-compartment model adopting the Michaelis-Menten type for the transfer of 99mTc-GSA from hepatic blood to receptor, and the other was a linear five-compartment model assuming a linear rate constant (P(2)*) for the transfer of 99mTc-GSA. The maximum removal rate obtained by the nonlinear model, P(2), was found to be independent of the change in acquisition time, while the maximum removal rate obtained by the linear model, P(2)*·Km, which was given by the product of P(2)* and the Michaelis constant Km, increased with shortening acquisition times from 40 to 20 min. For both models, the liver blood flow rate decreased with shortening acquisition time. The maximum removal rate and liver blood flow rate obtained by the linear model were significantly correlated with those obtained by the nonlinear model. It was concluded that linear model with an acquisition time of 20 min was applicable to liver scintigraphy with 99mTc-GSA. (author)

Full text:99mTc-tetrofosmin prone scintimammography was performed in 12 patients with palpable breast lesions and abnormal mammography findings. Right and left lateral prone and anterior supine views were obtained starting at 10 min of intravenous injection of 20 mCi 99mTc labelled tetrofosmin. Focal increased concentration of radiopharmaceutical as compared to surrounding normal breast tissue was considered positive for malignant disease. Patients underwent surgery with histopathological examination. 7 of the eight malignant lesions showed accumulation of 99mTc-tetrofosmin. Involved lymph nodes were also seen to concentrate the radiopharmaceutical. Four benign breast masses did not show focal 99mTc-tetrofosmin uptake. Initial results suggest that 99mTc-tetrofosmin could play a useful role in evaluation of breast tumours

The preparation and evaluation of three different 99mTc labelled peptides as third generation radiopharmaceuticals is presented. Lys3-Bombesin ([Lys3]BN), ubiquicidin 29-41(UBI 29-41) and Tyr3-octreotide (TOC) were prepared as instant kit formulations to be labelled by direct or indirect methods with 99mTc in order to evaluate in vivo prostate malignancies, infection processes and lung cancer respectively. Radiochemical purity of >93% was obtained. Also, high in vitro and in vivo stabilities and preservation of the molecular recognition were observed. It is demonstrated that 99mTc-EDDA/ HYNIC-[Lys3]BN detects GRP receptor positive tumours in mice, 99mTc-UBI 29-41 detects infection foci in humans and 99mTc-EDDA/HYNIC-TOC is useful in patients with lung cancer. (author)

The purpose of the current study was to clarify the myocardial kinetics of technetium-99m sestamibi when the latter is administered during reperfusion. Sestamibi has in the past been given to patients following thrombolytic therapy to document reperfusion and assess salvage. However, the factors which affect sestamibi kinetics during reperfusion are not clearly defined. In this study the left circumflex coronary artery was occluded for 2 h in six dogs (group 1) and for 3 h in six dogs (group 2), followed by reperfusion. Five additional dogs were not reperfused (group 3). Sestamibi was administered during reperfusion in groups 1 and 2, and during ongoing occlusion in group 3. Regional myocardial sestamibi activity was monitored for 3 h using miniature implanted radiation detectors and gamma camera imaging. Group 1 dogs had no infarcts, group 2 had moderate infarcts (mean: 13.9%), and group 3 had large infarcts (mean: 25.2%). Three-hour fractional myocardial clearances were significantly greater for reperfused infarcted (group 2) (0.23±0.02 SEM) and for nonreperfused infarcted myocardium (group 3) (0.24±0.02) compared to control (0.10±0.01) and reperfused noninfarcted myocardium (group 1) (0.07±0.02; P<0.01). Quantitative image analysis demonstrated a significant reduction in the left circumflex/left anterior descending count ratios from initial to final scans for group 2 (0.74±0.03 to 0.65±0.03, P<0.05), and a trend towards a reduction in the count ratios from initial to final scans for group 3 (0.38±0.04 to 0.30±0.04; P=0.06). Thus, probederived myocardial sestamibi kinetics following reperfusion do differentiate non-infarcted from infarcted myocardium. Although the detection of accelerated clearance can be demonstrated by quantitative analysis of gamma camera images in dogs, this may be technically difficult in clinical situations. (orig.)

Drug interactions with /sup 99m/Tc gluceptate resulting in altered biodistribution were studied using chart review and animal tests. Charts of nine patients who had abnormal gallbladder uptake of technetium /sup 99m/Tc gluceptate during a two-year period were reviewed to obtain data such as concurrent drug therapy, primary diagnosis, and laboratory values. Adult New Zealand white rabbits were then used for testing the biodistribution of technetium /sup 99m/Tc gluceptate when administered concurrently with possibly interacting drugs identified in the chart review--penicillamine, penicillin G potassium, penicillin V potassium, acetaminophen, and trimethoprim-sulfamethoxazole. Chart review revealed no conclusive patterns of altered biodistribution associated with other factors. The data did suggest the possibility that the five drugs listed above might cause increased hepatobiliary clearance of the radiopharmaceutical. Animal tests showed that i.v. penicillamine caused substantial distribution of radioactivity into the gallbladder and small bowel. Minimally increased gallbladder radioactivity occurred when oral acetaminophen and trimethoprim-sulfamethoxazole were administered concurrently. Oral and i.v. penicillins did not increase gallbladder activity. Penicillamine may cause substantial alteration of the biodistribution of technetium /sup 99m/Tc gluceptate.

In recent years the authors have reported on (99m)Tc(CO)3-labeled peptides that serve as carriers for biomolecules or radiopharmaceuticals to the tumors. In continuation of that work they report the synthesis of a pentapeptide (Met-Phe-Phe-Gly-His; pep-1), a hexapeptide (Met-Phe-Phe-Asp-Gly-His; pep-2), and a tetrapeptide (Asp-Gly-Arg-His; pep-3) and the attachment of 3-amino-1,2,4-triazole to the β carboxylic function of the aspartic acid unit of pep-2 and pep-3. The pharmacophores were radiolabeled in high yields with [(99m)Tc(CO)3(H2O)3](+) metal aqua ion, characterized for their stability in serum and saline, as well as in His solution, and found to be substantially stable. B16F10 cell line binding studies showed favorable uptake and internalization. In vivo behavior of the radiolabeled triazolyl peptides was assessed in mice bearing induced tumor. The (99m)Tc(CO)3-triazolyl pep-3 demonstrated rapid urinary clearance and comparatively better tumor uptake. Imaging studies showed visualization of the tumor using (99m)Tc(CO)3-triazolyl pep-3, but due to high abdominal background, low delineation occurred. Based on the results further experiments will be carried out for targeting tumor with triazolyl peptides. PMID:27093344

A new way for the preparation of 99mTc-stannous cooloid instant kit, its animal experimental results and its application to clinical practice were described. 500 mg sodium fluoride and 25 mg stannous chloride were dissolved in 50 ml sterile water, and the pH was adjusted to 6.4 with 0.05 mol/LHCl 0.5 millilitre of this solution was filtered into a vial and dryed under sterile condition. The kit can be used immediately after adding 2 ∼ 4 ml of 99mTcO4. It is suitable for intravenous administration as a imaging agent for liver or other organs of the reticuloerdothelial (RE) system. Distribution stadies of the 99mTc-stannous colloid in rats showed a rapid clearance of radioactivity from the blood stream and a subsequent rapid increase of radioactivity in the liver, up to approximately 90% of the injected dose. No toxic reactions were observed in rabbits at a dose of 1 ml of 99mTc-stannous colloid/kg

In recent years, imaging tumours with receptor specific biomolecules has been the focus of increasing interest. VIP has a high affinity for specific receptors that are expressed in high density on a large number of malignant tumours. VIP was modified (TP 3654) without compromising its biological activity, and labelled with 99mTc. Pharmacokinetics and feasibility studies were performed in three normal volunteers and 11 patients with a history of cancer. Imaging was performed for up to two h post-injection. Within 24 h after injection of 99mTc-TP 3654 (10-15 mCi/5 μg), approximately 70% of the tracer cleared through the kidneys, and 20% through the liver. Blood clearance was rapid. No adverse reaction was noted in any subjects. All known tumours were clearly delineated within 20 min. Findings were compared with the results of 99mTc-MIBI, CT, MRI, or histology. There was concordance in nine patients. In the other two, only the VIP scan was positive for tumours known to express VIP receptors. The early results of imaging tumours with 99mTc-VIP are promising and warrant further studies. (author)

Full Text Available 99mTc-MAG3 is a standard radiotracer for renal dynamic functional study. Despite its"nproperties for clinical uses, it has numerous technical limitations. 99mTc-EC is also a tubular"nradiotracer for renal imaging, which has not been used worldwide. In this study, the use of 99mTc-EC"nand 99mTc-MAG3 for renal functional study were compared."nMethods: Thirty five patients (20 male, 15 female; mean age of 34.63 ±10.69 years were entered in"nthe study. About 10 mCi of 99mTc-EC and 99mTc-MAG3 were administered in different days within 7"ndays intervals and serial images were obtained for 30 minutes. Serum creatinine and visual"nscintigraphic findings of all patients were within normal limits."nResults: In this study, the renal uptake of 99mTc-EC was significantly higher than 99mTc-MAG3 (6.20%"nvs 4.39% of the injected dose, while the hepatic activity of 99mTc-EC was significantly lower (307 vs"n439 mean pixel count, p<0.0001. Also the absolute values for some other quantitative parameters"nsuch as right and left kidney transit times and ERPF were different for each radiotracer. In spite of"nthese differences most quantitative parameters (except for right kidney transit time, liver uptake and"nTmax of both kidneys showed good correlations for both agents."nConclusion: The calculated ERPF with 99mTc-EC as compared to 99mTc-MAG3 is in closer proximity"nto the true values. Also the use of 99mTc-EC compared to 99mTc-MAG3 in clinic due to simplicity of"npreparation, higher stability, higher renal uptake, and lower hepatobiliary activity is better. Therefore"nthe use of 99mTc-EC as an appropriate substitute or ever preferred radiopharmaceutical for 99mTc-"nMAG3 radiopharmaceutical for renal function studies is recommended.

The aim of the present study was to compare 99mTc-DTPA plasma clearance kinetics with those of inulin, injected simultaneously, with respect especially to α2, rapidity of equilibration within the distribution volume and the components and size of the distribution volume. (orig./MG)

The aim of this work is the development of new radiopharmaceuticals for imaging infection and inflammation in human. Gatifloxacin (fluoroquinolone derivative) and cefepime (cephalosporine derivative) are antibiotics used to treat bacterial infections were investigated to label with one of the most important radioactive isotopes (technetium-99m). The reaction parameters that affect the labeling yield such as substrate concentration, stannous chloride dihydrate concentration, pH of the reaction mixture, and reaction time were studied to optimize the labeling conditions. Maximum radiochemical yield of 99mTc-gatifloxacin (90 ± 1.8%) complex was obtained by using 50 μg SnCl2 · 2H2O and 2.5 mg gatifloxacin at pH 10 while 99mTc-cefepime was prepared at pH 8 with a maximum radiochemical yield of 98 ± 1.4% by adding 99mTc to 5 mg cefepime in the presence of 50 μg SnCl2 · 2H2O. Biological distribution of 99mTc-gatifloxacin and 99mTc-cefepime was carried out in experimentally induced infection rats, in the left thigh, using Escherichia coli. Both thighs of the rats were dissected and counted and the ratio of bacterial infected thigh/contralateral thigh was then evaluated. T/NT for both 99mTc-gatifloxacin and 99mTc-cefepime was found to be 4.5 ± 0.3 and 8.4 ± 0.1, respectively, which was higher than that of the commercially available 99mTc-ciprofloxacin. The abscess to normal muscle ratio indicated that 99mTc-cefepime could be used for infection imaging. Besides, in vitro studies showed that 99mTc-cefepime can differentiate between bacterial infection and sterile inflammation. (author)

The preparation of 99Mo-,sup(99m)Tc generator based on the adsorption of 99Mo on hydrous zirconium oxide column, employing the in exchange technique, is described. The adsorption of 99Mo on hydrous zirconium oxide (HZO) and the separation of sup(99m)Tc, generated by the decay of 99Mo with saline solution, are analised. The sup(99m)Tc separation yield, pH of the eluted solution, aspect of the elution curve and the adsorption of 99Mo on hydrous zirconium oxide calcined at 8000C are studied. The chemical and radioactive purities of the final product are analysed and the variation of the elution yield for successive elutions is studied. (Author)

Primary spontaneous pneumothorax (PSP) occurs subsequent to a disruption in the continuity of visceral pleura and escape of air into the pleural space. The cause of PSP is most often the rupture of subpleural blebs or bullae. It is usually difficult to detect evidence of pulmonary pathology. The purposes of the present study were to investigate the changes of pulmonary alveolar epithelial permeability in patients with PSP as determined by Tc-99m DTPA aerosol lung scintigraphy, to assess whether or not some differences exist between apical and basal parts of the lungs, and to determine the relationship between the clearance rate of Tc-99m DTPA and the pulmonary function test (PFT) results, the recurrence rate of PSP, and the percentage of pneumothorax in affected lung. Thirteen PSP patients (two females, 11 males; mean age 32.5±11.8 years) with normal chest X-ray were studied. Thirteen healthy non-smoking volunteers (1 female, 12 males; mean age, 35.8±10 years) were selected as a control group. Tc-99m DTPA aerosol lung scintigraphy and PFT were performed in all patients and controls. Clearance rates (%/min) of Tc-99m DTPA aerosol in right and left lung field, and apical and basal parts of each lung were calculated from dynamic images for 15 min. There was no significant difference (p>0.05) between patients and controls, or between apical and basal parts of each lung. No correlation was found between the clearance rate of Tc-99m DTPA and PFT results, the recurrence rate of PSP, or the percentage of pneumothorax. This study demonstrates that pulmonary epithelial permeability is not altered in PSP patients; the clearance rate of Tc-99m DTPA shows no difference between apical and basal parts of each lung. (author)

The absorbed dose in the kidneys of adult patients has been assessed using the biokinetics of radiopharmaceuticals containing Tc{sup 99m} (DTPA) / Tc{sup 99m} (Mag3) or Tc{sup 99m} (Dmsa).The absorbed dose was calculated using the formalism MIRD and the Cristy-Eckerman representation for the kidneys. The absorbed dose to the kidneys due to Tc{sup 99m} (DTPA) / Tc{sup 99m} (Mag3), are given by 0.00466 mGy.MBq{sup -1} / 0.00339 mGy.MBq{sup -1}. Approximately 21.2% of the absorbed dose is due to the bladder (content) and the remaining tissue, included in biokinetics of Tc{sup 99m} (DTPA) / Tc{sup 99m} (Mag3). The absorbed dose to the kidneys due to Tc{sup 99m} (Dmsa) is 0.17881 mGy.MBq{sup -1}. Here, 1.7% of the absorbed dose is due to the bladder, spleen, liver and the remaining tissue, included in biokinetics of Tc{sup 99m} (Dmsa). (Author)

Soluble radioaerosols such as technetium-99m diethylene triamine pentacetate (DTPA) permit simple quantitative studies of alveolar-capillary permeability to be performed, since the submicronic aerosols are deposited mainly at the lung periphery and are cleared across the alveolar-capillary membrane. Regional alterations in permeability can also be noted using this radionuclide technique. We have measured the pulmonary epithelial permeability in normal subjects and the alteration in smokers, glue-sniffers, patients with inhalation burns, chronic obstructive pulmonary disease (COPD) and patients with lung metastases from thyroid cancer treated with radioiodine 131I. In the normal volunteers, the time taken for 50% of inhaled 99mTc DTPA to be cleared from the lungs (T1/2) was 66 minutes±1 sd of 12 mins. The smokers had a mean T1/2 of 20 mins±1 sd 4 min. In the hard-core glue-sniffing group, the majority were smokers who had stopped smoking and glue-sniffing for periods varying from 1 day to 42 days, and it was possible to note the changes in clearance times against period of abstinence. In the patients with inhalation burns, there was change in lung clearance arising from pulmonary epithelial damage; these patients showed increased rate of clearance (short T1/2) with mean T1/2 of 36 min±1 sd of 11 mins, while the retention images revealed regional lung damage in moderately severe inhalation burns. Twenty-four patients with COPD had inhalation scans done with Tc-99m tin colloid radioaerosol, and these images were compared with the perfusion lung scans done with 99mTc macroaggregated albumin (MAA); in general the perfusion images matched the defects noted in the inhalation scans. The 99mTc DTPA clearance rate in these patients was normal i.e. T1/2=78±14 mins. In the thyroid cancer patients with lung metastases, who had high doses of radioiodine treatment, the T1/2 values were normal or prolonged slightly, mean T1/2=76 min±23. (author)

We report here on the use of the lipophilic cationic complex technetium-99m sestamibi (99mTc-MIBI), employed as an indicator of increased cellular density and metabolic activity, to evaluate Gaucher cell infiltrates in the bone marrow; 99mTc-hexametazime (99mTc-HMPAO) was also employed, as a pure indicator of lipidic infiltration in the bone marrow. A 67-year-old patient with known type 1 Gaucher's disease presented with a painful left hip and knee and difficulty in gait subsequent to traumatic fracture of the left femoral neck that had required implant of a fixation screw-plaque. Bone scan with 99mTc-methylene diphosphonate revealed reduced uptake at the distal metaphyseal-epiphyseal femoral region. In addition, whole-body maps and spot-view acquisitions of the thighs and legs were recorded at both 30 min and 2.5 h after the injection of 99mTc-MIBI: the scintigraphic pattern clearly showed increased uptake at several sites involved by Gaucher deposits in the bone marrow (both knees, with variable intensity in different areas), matching the bone changes detected by conventional x-ray. The target to non-target ratios slowly decreased with time, from an average value of 2.25 in the early scan to an average value of 2 in the delayed scan. The lipid-soluble agent 99mTc-HMPAO exhibited a superimposable scintigraphic pattern of accumulation at the involved sites, though with lower target to non-target ratios (1.27-1.48). The results obtained in this patient suggest a potential role of 99mTc-MIBI in the scintigraphic evaluation of Gaucher's lipid deposits in the bone marrow. If the results are confirmed in other patients, this radiopharmaceutical would offer clear advantages over 133Xe because of its wider availability and greater practicality (i.v. administration of 99mTc-MIBI versus inhalation of 133Xe, and use of a single gamma camera instead of two as with 133Xe). (orig.). With 3 figs

Technetium-99m hexakis-2-methoxyisobutyl-isonitrile (MIBI), 99mTc-tetrofosmin and 99mTc-Q12 were all introduced for myocardial imaging but found additional applications as they are taken up by different tumours, enabling imaging of these lesions in patients. The aim of this study was to compare the uptake characteristics of these compounds in vitro in the human adenocarcinoma breast cell lines MCF-7 and ZR-75. It was shown that 99mTc-MIBI had the highest cellular uptake (15.9%±0.5% dose/mg protein after 60 min in MCF-7, and 14.2%±0.4% dose/mg protein in ZR-75), followed by 99mTc-tetrofosmin (6.8%±0.6% dose/mg protein in MCF-7, and 8.2%±0.2% dose/mg protein in ZR-75) and 99mTC-Q12 (3.2%±0.1% dose/mg protein in MCF-7, and 3.5%±0.3% dose/mg protein in ZR-75 cells). For all three compounds tenfold differences in specific activity did not influence total cell-associated radioactivity. Uptake of 99mTc-MIBI and 99mTc-tetrofosmin was obviously lower at 4 C than at 37 C, whereas 99mTc-Q12 uptake showed only slight temperature dependence. When uptake was compared in cells grown to different cell densities (1 mg/ml cellular protein versus 0.3 mg/ml), no differences in uptake were detected when uptake was corrected for the amount of cellular protein present in the dishes. Furthermore, for all compounds it was shown that cellular radioactivity decreased rapidly after washing. Apart from the differences in cellular uptake of the three compounds after 60 min, no differences in residual cellular radioactivity after washing were found between the different compounds when expressed as a percentage of their 60-min uptake, suggesting that the efflux process of the radiolabelled compounds was similar. The differences in cell-associated activity after 60 min were thus presumably caused by differences in uptake. (orig./MG)

The aim of the present work was to evaluate three agents selected in this CRP for their possible role as 99mTc labelled infection imaging agents: human neutrophil elastase inhibitor (HNE2), Ubiquicidin (UBI 29-41) and Ethylene diamine tetraacetic acid biotin monomer (EB1). 99mTc labelling of EB-1 was carried out by direct labelling method with a yield of 90-95%. UBI was labelled by direct labelling as well as indirect labelling method using cyclic DTPA and HYNIC as conjugates with labelling efficiency of >95% in both cases, while HNE-2 was labelled only by indirect method and >96% labelling with 99mTc could be achieved. Chromatographic studies like ITLC, paper chromatography and HPLC were carried out for radiochemical separation and for determining the labelling yields. Kit formulations were also developed for these agents. Since availability of HNE-2 was doubtful detailed study of 99mTc-UBI (29-41) involving cysteine challenge, in vitro binding with bacteria as well as infection imaging in mice and rabbits was carried out. Experimental thigh muscle infection was induced by injecting 2x108 CFU of live S. aureus or E. coli bacteria into right thigh muscle of rabbits while turpentine oil and formalin killed S.aureus were utilized for inducing sterile thigh muscles inflammation. Significantly higher (p99mTc-UBI (29--41) was seen at sites of S.aureus infected subjects (T/NT ratio 2.2 ± 0.5) as compared to E. coli (T/NT ratio 1.7±0.4). Maximum tracer accumulation was seen at 60 min post injection followed by gradual decline. No accumulation of 99mTc-UBI was observed in thighs of rabbits injected with either turpentine oil or killed S.aureus with significant lower T/NT ratios (p99mTc-UBI 29-41 scintigraphy is a good technique for differentiating infection with S. aureus and E. coli. This study can be extended to clinical study after toxicity clearance of 99mTc UBI 29-41. (author)

99mTc-labelled d,l-cyclobutylpropylene amine oxime (99mTc-CBPAO) has been developed as a brain imaging agent for single photon emission tomography (SPET). 99mTc-CBPAO can be prepared using a simple labelling procedure suitable for routine clinical use. It has a high in vitro stability, as has been demonstrated by high-pressure liquid chromatography (HPCL) analysis. This shows that 3 h after labelling, less than 5% of the primary lipophilic complex which is capable of crossing the blood-brain barrier (BBB) converts to a secondary hydrophilic complex. Brain uptake (% dose/g wet tissue) of 99mTc-CBPAO, determined at 5 and 30 min after injection in two groups of six adult male Sprague-Dawley rats, was found to be 0.74±0.06 and 0.73±0.13 (mean±SD), respectively. These values are not significantly different from those obtained repeating the experiment with 99mTc-labelled hexamethylpropylene amine oxime (99mTc-HMPAO) (0.72±0.15 at 5 min and 0.88±0.24 at 30 min after injection). Since the rat brain uptake of 99mTc-CBPAO remained unchanged for a period of time suitable for tomographic study, the comparison of the two tracers was extended to two groups of ten patients. The latter were affected by neurological and psychiatric disorders and were studied with SPET. Human brain uptake (% dose/cc cortical grey matter) of 99mTc-CBPAO and 99mTc-HMPAO were 3.04±0.57 and 4.22±0.46 (mean x 10-3±SD x 10-3), respectively, with a 32% significant difference. In two other groups of five patients, the first transit time-activity curves of the two tracers were compared. From the analysis of these curves we suggest that 99mTc-CBPAO has a higher binding effect on blood components and/or a higher degradation rate in blood than that of 99mTc-HMPAO. This may account for the reduced human brain uptake. In conclusion, SPET images of 99mTc-CBPAO reflect blood perfusion, and they have a good diagnostic quality. The main advantage of 99mTc-CBPAO is its in vitro stability; however, 99m

The purpose of this study was to assess the potentials of 99mTc MAG3 to replace universally used 99mTc-DTPA as a routine renal agent. Five patients with different nephrological problems were first studied with 99mTc MAG3 and then reinvestigated with 99mTc-DTPA two to seven days later. Renal MAG3 gamma camera images were found to be almost identical with those of 99mTc-DTPA images except high hepatic and splenic uptake of the former compound in four out of five patients (80%) irrespective of kidney function. MAG3 and DTPA renograms showed identical differential renal uptake function (r=0.87) with slightly higher uptake in right kidneys. Time to reach the peak correlated well (r=0.91). Time to reach half maximum renal activity was also found to be almost identical (r=0.97) for MAG3 and DTPA. It was felt that the age old 99mTc-DTPA is as good a compound as 99mTc MAG3 with regard to imaging and assessment of renal uptake, drainage and differential renal functions. 99mTc-DTPA is much cheaper, readily available in India and stable to suit the logistics in a busy nuclear medicine department for routine renography. (author). 10 refs., 2 figs., 3 tabs

Case report of a patient with hypercalcemia and suspected parathyroid adenoma. Because of a previous strumectomy a precise preoperative localization of the suspected parathyroid adenoma was demanded. Tc-99m-tetrofosmin scintigraphy in double phase technique failed to detect a parathyroid adenoma by failing to show a region of increased focal uptake with delayed washout in relation to the thyroid gland. Only comparison of the Tc-99m-tetrofosmin images with a Tc-99m-pertechnetate scan revealed a right caudal parathyroid adenoma. A double phase Tc-99m-MIBI study of the same patient was able to localize this parathyroid adenoma without the need of a corresponding Tc-99m-pertechnetate scintigraphy due to a differential washout with persistent focal uptake in the parathyroid adenoma and a progressively decreasing uptake in the thyroid tissue. This case indicates that Tc-99m-tetrofosmin is a suitable agent for parathyroid imaging only if used together with Tc-99m-pertechnetate but is seems to lack the differential washout characteristics of Tc-99m-MIBI according parathyroid gland and thyroid gland. (orig.)

Hypoxia, as a common phenomenon in solid tumors, is of interest for its relationship with resistance to tumor therapies and malignant progression of tumor. The noninvasive nuclear medical imaging technique using hypoxia markers is an important method for the detection of tumor hypoxia. The aim of current study is designing tumor hypoxia markers with hypoxia selectivity and improved properties. Two MAG{sub 3}-based bisnitroimidazole compounds were synthesized and purified by semi-preparative HPLC. Both the MAG{sub 3} derivatives were labeled with {sup 99m}Tc-oxo-technetium core via stannous tartrate exchange method in high yields (> 95%). The {sup 99m}Tc-MAG{sub 3} complexes were stable at 37 C, 4 h after preparation, and were more hydrophilic than {sup 99m}Tc-MAMA complexes. As biodistribution results showed, clearances of background activity for both the complexes were fast and they were excreted mainly through the hepatobiliary tract and part of renal tract. Although tumor uptakes of {sup 99m}Tc-MAG{sub 3}-B2NIL were lower than those of {sup 99m}Tc-MAG{sub 3}-B4NIL, tumor-to-blood ratios of {sup 99m}Tc-MAG{sub 3}-B2NIL showed an increasing trend and were better than those of {sup 99m}Tc-MAG{sub 3}-B4NIL after 2 h due to their different blood clearances. Tumor-to-muscle ratios of {sup 99m}Tc-MAG{sub 3}-B2NIL and {sup 99m}Tc-MAG{sub 3}-B4NIL were similar. Comparing with {sup 99m}Tc-MAMA complexes, {sup 99m}Tc-MAG{sub 3}-B2NIL with better tumor-to-blood ratios exhibits improved feature for hypoxia imaging, though it has lower tumor uptake than {sup 99m}Tc-MAMA complexes. (orig.)

Hypoxia, as a common phenomenon in solid tumors, is of interest for its relationship with resistance to tumor therapies and malignant progression of tumor. The noninvasive nuclear medical imaging technique using hypoxia markers is an important method for the detection of tumor hypoxia. The aim of current study is designing tumor hypoxia markers with hypoxia selectivity and improved properties. Two MAG3-based bisnitroimidazole compounds were synthesized and purified by semi-preparative HPLC. Both the MAG3 derivatives were labeled with 99mTc-oxo-technetium core via stannous tartrate exchange method in high yields (> 95%). The 99mTc-MAG3 complexes were stable at 37 C, 4 h after preparation, and were more hydrophilic than 99mTc-MAMA complexes. As biodistribution results showed, clearances of background activity for both the complexes were fast and they were excreted mainly through the hepatobiliary tract and part of renal tract. Although tumor uptakes of 99mTc-MAG3-B2NIL were lower than those of 99mTc-MAG3-B4NIL, tumor-to-blood ratios of 99mTc-MAG3-B2NIL showed an increasing trend and were better than those of 99mTc-MAG3-B4NIL after 2 h due to their different blood clearances. Tumor-to-muscle ratios of 99mTc-MAG3-B2NIL and 99mTc-MAG3-B4NIL were similar. Comparing with 99mTc-MAMA complexes, 99mTc-MAG3-B2NIL with better tumor-to-blood ratios exhibits improved feature for hypoxia imaging, though it has lower tumor uptake than 99mTc-MAMA complexes. (orig.)

The kinetic data of two different sup(99m)Tc-Sn-pyrophosphate compounds (compound A and B) were evaluated in non-adult rats. Only compound A concentrated in bone. Both compounds dispersed rapidly in the intravascular as well as the extravascular space. The plasma protein bond of both compounds increased with time after injection and impaired both the renal clearance of both compounds and the bone clearance of compound A. The renal clearance of both compounds was somewhat above that of 51Cr-EDTA. It is concluded that compound A and B is mainly excreted by glomerular filtration. About one fourth of the glomerular filtrate of compound B is reabsorbed and accumulated by the tubular cells. (orig.)

Biologic distribution of p- [(bis-carboxymethylaminomethyl carboxyamino)] hippuric acid (PAHIDA) labeled with sup(99m)Tc in Wistar rats, showed a selective renal uptake among the other organs and tissues. The compound is predominantly eliminated by urinary tract, with small enterohepatic percent of excretion Chromatographic analysis of urine showed the product and possible metabolites. PAHIDA- sup(99m)Tc blood clearance is relatively rapid and a good percent is transported by plasmatic proteins. The percent binding to the erythrocytes is significant after one hour, this is due probably to hydrolysed technetium. The extrapolation of the plasmatic curve denoted the existence of three exponentials, suggesting a model with three compartments: central or intravascular and two peripherics or extravasculars - rapid and slow exchange (retention). Exponential's half life and the transfer constant (k) among the compartments were determined. The compound retention was reaffirmed by whole body determination. The decomposition of the curve in two exponentials allowed to assess the component's half-life. The compartmental model proposed in agreement with the experimental results, showed the complex retention that may be related the binding with the blood components, the possibility of renal metabolization or a structural impediment in the interaction with the tubular cells receptors. (author)

Measurements were made of the concentration of Tc-99m activity in samples of breast milk following an administration of Tc-99m DTPA aerosol for a lung ventilation image and one of Tc-99m MAA for lung perfusion. The activity was 222 nCi/ml of milk (8.2 kBq/ml) at 2 hr after the MAA injection, and it was found to be excreted exponentially with an effective half-life of 4.6 hr. There was a small incorporation of Tc-99m into breast-milk protein. The authors conclude that the combined use of these two Tc-99m agents did not indicate the interruption of breast feeding beyond 24 hr after administration of the MAA, and that for an aerosol ventiliation study alone, breast feeding need not be interrupted for more than 4 hr after the test

Chrysamine G (CG), an analogue of Congo red, is known to bind in vitro to the β-amyloid protein (Aβ 10-43) and to homogenates of several regions of the brain of Alzheimer's disease (AD) patients. We synthesised a conjugate of 2-(acetamido)-CG with a bis-S-trityl protected monoamide-monoaminedithiol (MAMA-Tr2) tetraligand, which was efficiently deprotected and labelled with a 75% yield with technetium-99m, to obtain 99mTc-MAMA-CG. In mice, 99mTc-MAMA-CG was cleared mainly by the hepatobiliary system, resulting in a fast blood clearance. Brain uptake of 99mTc-MAMA-CG was low. Co-injection with the blood pool tracer iodine-125 human serum albumin (125I-HSA) demonstrated a brain/blood activity ratio for 99mTc-MAMA-CG that was significantly higher than that for 125I-HSA (t test for dependent samples, P99mTc-MAMA-CG to cross the blood-brain barrier. In vitro autoradiography demonstrated pronounced binding of 99mTc-MAMA-CG to β-amyloid deposits in autopsy sections of the parietal and occipital cortex of an AD patient as compared with controls. Adding 10 μM Congo red during incubation displaced the binding of 99mTc-MAMA-CG. Congo red staining and autoradiography identified the same lesions. 99mTc-MAMA-CG seems to bind selectively to β-amyloid deposition in human brain parenchyma and blood vessels in vitro and thus might be a lead compound for further development of a useful tracer agent for the in vivo diagnosis of Alzheimer's disease. (orig.)

Conjugates of two somatostatin analogues, octreotide and RC-160, with HYNIC were synthesized, characterized and purified by reverse phase HPLC. Radiolabelling of the conjugates with 99mTc was achieved using tricine as co-ligand. High labelling efficiencies were obtained and 99mTc peptides with high radiochemical purity were found when analysed both by ITLC and HPLC. In vitro stability of 99mTc-peptides in human serum and towards cysteine challenge was determined by Cellogel electrophoresis and HPLC after ultrafiltration of serum solution through a 20 kDa cut off membrane. Biodistribution studies were performed in healthy mice at 5 and 30 minutes and 1, 2, 4 and 24 h post-injection. Urine and blood samples were collected at sacrifice time. Samples of urine and ultrafiltrate murine serum were analysed by electrophoresis and reverse phase HPLC in order to get some information about radiocompounds metabolism. Biological distribution of 99mTc octreotide was also assayed in mice pre-treated with an excess of unlabelled peptide. From our results we conclude that this labelling method led to stable 99mTc complexes both in vitro and in vivo when high specific activities (37-72 GBq/μmole) were used. Biodistribution studies of both 99mTc-peptides indicated a radioactivity distribution profile with significant differences especially in the liver uptake that is higher for 99mTc RC-160. However, a rapid blood clearance was obtained for both radiolabelled peptides, and the urine analysis indicated that 99mTc peptide is mostly excreted as the initial complex. Pre-treatment with unlabelled peptide did not affect renal excretion of 99mTOC but pancreas and intestine radioactive uptake was significantly lower, indicating saturation of somatostatin receptors and selective uptake. (author)

We investigated the biokinetics of 99mTc-sestamibi in the thyroid of euthyroid volunteers (EVs) and in patients with autoimmune thyroid diseases and determined the best time interval between 99mTc-sestamibi injection and calculation of uptake. Forty EVs, 30 patients with Graves' disease (GD), 15 patients with atrophic Hashimoto's thyroiditis (AHT) and 15 patients with hypertrophic Hashimoto's thyroiditis (HHT) underwent 99mTc-sestamibi thyroid scintigraphy. Dynamic images were acquired for 20 min, and static images were obtained 20 min, 60 min and 120 min post injection. Five-, 20-, 60- and 120-min uptake, time to maximal uptake (Tmax) and T1/2 of tracer clearance were calculated. Thyroid hormones and antibodies were measured. 99mTc-pertechnetate uptake was investigated in GD patients. Tmax was approximately 5 min in all four groups. The mean T1/2 value for EVs was similar to the GD value and lower than the HHT and AHT values. The mean (±SD) 5-min uptake was 0.13% (±0.05%) for EVs. The 5-min uptake in GD was higher than that in EVs(P99mTc-pertechnetate uptake (r=0.68). Uptake in HHT was higher than that in AHT (P=0.0003) and EVs (P=0.002). Uptake in AHT was lower than uptake in EVs (P=0.0001). Five minutes is the optimal time interval between 99mTc-sestamibi injection and calculation of thyroid uptake. Five-minute uptake differentiates euthyroid individuals from GD patients. There is a high correlation between 99mTc-sestamibi and 99mTc-pertechnetate uptake in GD. The reduced 99mTc-sestamibi uptake in AHT patients is probably due to glandular destruction and fibrosis. Inflammatory infiltrate and high mitochondrial density in thyrocytes possibly explain the increased uptake in GD and HHT. (orig.)

The subject of the chemistry of 99mTc-radiopharmaceuticals consists of a collection of bits and pieces of information without a unifying theme. Since the initial impetus to the field of organ imaging was provided by radiochemists, nuclear chemists, and clinician-investigators, using easily prepared 99mTc-compounds from available off-the-shelf ligands, complete chemical characterization was not carried for the 99mTc-radiopharmaceuticals and their metabolites. The influx of coordination, organic, and analytic chemists and their systematic studies clarified some of the structures of these tracers, and promoted the general synthetic methods of a variety of ligands and the corresponding 99mTc-chelates as well as understanding of the nature of their metabolites. Although major developments for organ-imaging radiopharmaceuticals had been made, future studies will result in the simplified methodology of protein-labeling, fine-tuning of the currently available radiopharmaceuticals for higher organ-extraction, and replacement of expensive 123I-labeled tracers with the corresponding 99mTc-tracers. In general, the Tc-complexes are thermodynamically less stable and kinetically more labile than the corresponding Re-complexes. The well established chemistry of Re-compounds, the similarity of Tc-chemistry to that of Re compounds, and structure-activity relationships of a few classes of 99mTc-labeled compounds, may promote the development of new generation of 99mTc-labeled radiopharmaceuticals.69 references

{sup 99m}Tc-sestamibi is a single-photon emission computed tomography (SPECT) radiotracer that was introduced into clinical routine for myocardial perfusion imaging more than two decades ago. Although today the main application of {sup 99m}Tc-sestamibi SPECT remains the imaging of myocardial perfusion, it is also an accepted and well-proven imaging technique for a variety of oncologic and non-oncologic applications, including brain, breast, and thyroid cancer and thyroid and parathyroid adenoma. Its efficacy in a range of indications ensures that {sup 99m}Tc-sestamibi SPECT will remain widely used despite the rapid diffusion of 18F-FDG PET. {sup 99m}Tc-Sestamibi - Clinical Applications provides a detailed and informative overview of almost all the oncologic and non-oncologic applications of {sup 99m}Tc-sestamibi SPECT, including several relatively rare indications. Different disease-related protocols for {sup 99m}Tc-sestamibi SPECT are presented, and for each disease a comprehensive summary of the relevant pathology and epidemiology is provided. Throughout, there is a strong emphasis on the practical aspects of use of this popular tracer, including instructions for the preparation of several commercially available tracer kits. Clinical practitioners will find this book to be an invaluable guide to the application and benefits of {sup 99m}Tc-sestamibi SPECT in both the inpatient and the outpatient setting. (orig.)

A new method is described in which Pt-Sn or Sn-Sn electrodes are used to activate /sup 99m/TcO4-. The /sup 99m/Tc is incorporated into phytic acid by stannous ion released from a tin anode by the corrosive reaction. The most suitable pH for labeling phytic acid by this method was below 5 and the /sup 99m/Tc-phytate formed could be precipitated with Ca+2 at a pH above 3.5. Though /sup 99m/Tc-phytate is soluble in aqueous solution, it forms an insoluble species with Ca+2 in vivo and is trapped in the reticuloendothelial system. More than 93 percent of the /sup 99m/Tc-phytate localized in the liver of mice; here its biologic half-time is about 112 hr. The /sup 99m/Tc-phytate prepared by this method promises to be useful as a liver-scanning agent. Since our method does not require an applied electric potential, it appears to be one of the most convenient methods for labeling compounds with /sup 99m/Tc

Tc-99m ciprofloxacin is available for imaging infection. However, there has been no study on employing single photon emission computed tomography (SPECT) with using Tc-99m ciprofloxacin to image active pulmonary tuberculosis. Therefore, we conducted this study to assess the efficacy of Tc-99m ciprofloxacin SPECT for imaging active pulmonary tuberculosis. Twenty-one participants were enrolled in this prospective study. They were divided into two groups according to the clinical and radiological assessment. Group one (Gr. 1) consisted of five normal volunteers and six patients with inactive pulmonary tuberculosis. Group two (Gr. 2) consisted of ten patients with active pulmonary tuberculosis. SPECT was performed 3 h after injecting 555 MBq (15 mCi) of Tc-99m ciprofloxacin. The findings of Tc-99m ciprofloxacin SPECT were interpreted by a nuclear medicine specialist and then the results were analyzed according to the patients' clinical and radiological classifications. The results of Tc-99m ciprofloxacin SPECT were as follows: eight true-positive cases, ten true-negative cases, one false-positive case and two false-negative cases. The sensitivity and specificity was 80.0% and 90.0%, respectively. The positive predictive value was 88.9% and the negative predictive value was 83.3%. Conclusions Tc-99m ciprofloxacin SPECT is feasible for imaging active pulmonary tuberculosis. It is a useful nuclear-imaging method for discriminating between the active and inactive tuberculosis states in patients with a past medical history of pulmonary tuberculosis.

Tc-99m ciprofloxacin is available for imaging infection. However, there has been no study on employing single photon emission computed tomography (SPECT) with using Tc-99m ciprofloxacin to image active pulmonary tuberculosis. Therefore, we conducted this study to assess the efficacy of Tc-99m ciprofloxacin SPECT for imaging active pulmonary tuberculosis. Twenty-one participants were enrolled in this prospective study. They were divided into two groups according to the clinical and radiological assessment. Group one (Gr. 1) consisted of five normal volunteers and six patients with inactive pulmonary tuberculosis. Group two (Gr. 2) consisted of ten patients with active pulmonary tuberculosis. SPECT was performed 3 h after injecting 555 MBq (15 mCi) of Tc-99m ciprofloxacin. The findings of Tc-99m ciprofloxacin SPECT were interpreted by a nuclear medicine specialist and then the results were analyzed according to the patients' clinical and radiological classifications. The results of Tc-99m ciprofloxacin SPECT were as follows: eight true-positive cases, ten true-negative cases, one false-positive case and two false-negative cases. The sensitivity and specificity was 80.0% and 90.0%, respectively. The positive predictive value was 88.9% and the negative predictive value was 83.3%. Conclusions Tc-99m ciprofloxacin SPECT is feasible for imaging active pulmonary tuberculosis. It is a useful nuclear-imaging method for discriminating between the active and inactive tuberculosis states in patients with a past medical history of pulmonary tuberculosis.

Perfusion lymphoscintigraphy was performed by subcutaneous injection of 7.4 MBq (0.2 mCi) {sup 99m}Tc-human serum albumin ({sup 99m}Tc-HSA) in 25 patients with uterine cancer treated by operation and/or irradiation. Radioactivity at the injection site was counted for 3 min at 10 min (a) and at 3 hr (b) after injection, and the clearance of {sup 99m}Tc-HSA was defined as (1-(b)/(a))x100(%) ((a) and (b) were corrected for decay of the isotope). The clearance in legs with lymphedema was significantly more delayed than those in legs without lymphedema in patients treated with both operation and irradiation (16.6{+-}7.7% vs 34.9{+-}9.3%; p<0.01) and in patients treated with radiation therapy alone (33.1{+-}7.4 vs 48.0{+-}5.6; p<0.01). The clearances in edematous legs in a case which had developed venous occulusion after operation were 44.2% and 41.7%, which were almost the same as those in the non-edematous patients treated with operation alone. Clearance in patients treated with both operation and irradiation were significantly more delayed than those in patients treated with a single modality of operation or irradiation (30.1{+-}11.4% vs 41.9{+-}8.9%, 42.0{+-}9.7%, respectively; p<0.01). Radiation doses at points B were well correlated with clearance of {sup 99m}Tc-HSA (p<0.05). These data suggest that perfusion lymphoscintigraphy using {sup 99m}Tc-HSA is useful for evaluating the patients with lymphedema and for differentiating it from the edema caused by the other mechanisms. It is also suggested that radiation dose is one of factors in the occurrence of lymphedema. (author).

The asialoglycoprotein receptor (ASGP-R) is expressed on liver hepatocytes. Chitosan conjugates of galactose have shown to be specifically taken up by liver parenchymal cells via ASGP-R. In this study, Tc-99m hydrazino nicotinamide (HYNIC)-galactosylated chitosan (HYNIC-GC) was synthesized and evaluated as a targeted agent for the imaging of hepatocytes. GC was obtained after coupling of lactobionic acid as the galactose moiety and coupled with HYNIC. HYNIC-GC was radiolabeled with Tc-99m using stannous chloride and tricine as reducing agent and coligand respectively. Hepatic uptake property of Tc-99m HYNIC-GC was studied in female Balb/C mouse. Tc-99m HYNIC--GC and Tc-99m HYNIC-Chitosan as a control were intravenously injected into mice. Receptor binding was identified by coinjection with 50 mM and 80mM free galactose respectively. Biodistribution was determined at three different time points. The level of galactose substitution was 7.6%. Labeling efficiency was >90% both in vitro and serum up to 24 h. Tc-99m HYNIC-GC injected via tail vein of mice showed high selectivity of liver. On the other hands, Tc-99m HC without galactose group showed low uptake (Fig. 1A, 1B). Hepatic uptake of Tc-99m HYNIC-GC was dramatically blocked by 50 mM and 80 mM free galactose coinjection (Fig. 1C, 1D). The liver accumulated about 14 percent injected dose per gram (%ID/g) up to 120 min after injection. Tc-99m HYNIC-GC showed specific and rapid targeting to liver. It is a promising specific radiopharmaceutical with potential applications in the imaging of liver parenchymal cells.

The asialoglycoprotein receptor (ASGP-R) is expressed on liver hepatocytes. Chitosan conjugates of galactose have shown to be specifically taken up by liver parenchymal cells via ASGP-R. In this study, Tc-99m hydrazino nicotinamide (HYNIC)-galactosylated chitosan (HYNIC-GC) was synthesized and evaluated as a targeted agent for the imaging of hepatocytes. GC was obtained after coupling of lactobionic acid as the galactose moiety and coupled with HYNIC. HYNIC-GC was radiolabeled with Tc-99m using stannous chloride and tricine as reducing agent and coligand respectively. Hepatic uptake property of Tc-99m HYNIC-GC was studied in female Balb/C mouse. Tc-99m HYNIC--GC and Tc-99m HYNIC-Chitosan as a control were intravenously injected into mice. Receptor binding was identified by coinjection with 50 mM and 80mM free galactose respectively. Biodistribution was determined at three different time points. The level of galactose substitution was 7.6%. Labeling efficiency was >90% both in vitro and serum up to 24 h. Tc-99m HYNIC-GC injected via tail vein of mice showed high selectivity of liver. On the other hands, Tc-99m HC without galactose group showed low uptake (Fig. 1A, 1B). Hepatic uptake of Tc-99m HYNIC-GC was dramatically blocked by 50 mM and 80 mM free galactose coinjection (Fig. 1C, 1D). The liver accumulated about 14 percent injected dose per gram (%ID/g) up to 120 min after injection. Tc-99m HYNIC-GC showed specific and rapid targeting to liver. It is a promising specific radiopharmaceutical with potential applications in the imaging of liver parenchymal cells

Labeling of scorpion venom (SV) was successfully achieved with 99mTc using direct chelating method. Venom was labeled with 99mTc using stannous chloride as reducing agent. Preliminary studies were done to establish the optimum conditions for obtaining the highest yield of the labeled venom. The labeling technique is effective, as a maximum labeling yield (97 %) was obtained after 30-min reaction time by using 80 μg SV in phosphate buffer of pH 7 and 25 μg Sncl2·2H2O at room temperature. Venom was injected into normal mice to determine the excretion pathway. Biodistribution studies in normal mice with SV shows rapid clearance of the venom from blood and tissue except for kidneys. The improvement of the immunotherapeutic treatment of envenomation requires a better knowledge of the biological actions of the SV since tissue distribution studies are very important for clinical purpose. (author)

This paper describes a method for labelling red blood cells with 99mTc in vitro, using electrolytically generated stannous ions as the reducing agent for 99mTc-pertechnetate. A labelling of 95% was found. A method for the in vivo labelling of red blood cells is also reported. This involves an injection of a stanno-DTPA-complex followed 20 minutes later by a 99mTc-pertechnetate solution scintillation camera images show more background activity when the in vivo method of labelling is used

The authors report the preparation of 99mTc-ECD instant kit, and a comparison of the instant kit with the ligand exchange kit. The radiochemical purity, stability, animal experiment and preliminary clinical trial showed that the instant kit possessed the following advantages: (1) The labelling yield (greater than 95%) and stability of 99mTc-ECD (the liberation of 99mTc 5 hr after preparation was less than 1%) were high; (2) The labelling method was simple, convenient and effective; (3) The quality of brain SPECT images was good. This instant kit is more suitable for the clinic application than the 2-step kit

Full text: High uptake of bone-seeking radiopharmaceuticals in malignant bone lesions is a prerequisite for adequate bone scanning. Visual image analysis is impaired due to high soft-tissue activity with currently available [99mTc]-EDTMP-kits. This study aimed to compare carrier-added [99mTc]-EDTMP with carrier-free [99mTc]-EDTMP and [99mTc]-DPD preparations in clinical routine. 15 μg and 150 μg perrhenic acid respectively were added to [99mTc]-pertechnetate (>6 GBq in 3 ml phys. saline). The solution was then transferred into a vial, containing 1 mg of EDTMP, 3.6 mg stannous(II)chloride and 10 mg ascorbic acid under inert conditions. Under vigorous stirring the reaction mixture was heated to 45 oC for 10 min. After cooling down to room temperature the labelling mixture was sterile filtrated (millipore 0.22 μm). Quality control was performed using radio-ITLC (Whatman SG; acetone or ethanol: Rf perrhenate/pertechnetate 0.87, colloid/product 0.05; phys. saline: Rf colloid 0.00, perrhenate/pertechnetate and product 0.9) allowing rapid and efficient assessment of the product. Carrier free [99mTc]-EDTMP and [99mTc]-DPD were prepared according to instructions of the manufacturer. Clinical studies were performed in 29 patients according to a routine bone scanning protocol by injecting 700-800 MBq of the respective tracer and whole body imaging 3 h thereafter. Radiochemical purity and radiochemical yield relied on various parameters such as concentration of carrier and reducing agent and reaction conditions (pH, reaction time, temperature). Means of the labelling yield were 22 % for the preparation using 150 μg of carrier (5 preparations), 80 % for the preparation using 15 μpg of carrier (10 preparations) and 91 % for the carrier free products (5 preparations). Radiochemical purity was >96 % in all experiments. Colloid was formed in very low amounts, and was completely removed by sterile filtration. In clinical studies quantitative analysis demonstrated a significant

Transjugular intrahepatic portosystemic shunt (TIPS), a new therapeutic method, has been performed widely for the treatment of portal hypertension. TIPS produces a decrease in the portal blood flow to the hepatic parenchyma, which is considered to cause a reduction in hepatic functional reserve. To evaluate the changes in hepatic functional reserve after TIPS, we performed technetium-99m DTPA-galactosyl human serum algumin (99mTc-GSA) hepatic scintigraphy before and after TIPS in eight male patients, ranging in age from 54 to 72 years (mean 62.2 years). Two quantitative indices - blood clearance index (uptake ratio of the heart at 15 min to that at 3 min, HH15) and hepatic accumulation index (uptake ratio of the liver to the liver plus heart at 15 min, LHL15) - were calculated from the time-activity curves of the heart and liver. Early and late uptake constant indices (early and late KU) were also calculated from the time-activity curves of the heart and liver by means of Patlak plot. The values of HH15, LHL15 and late KU deteriorated after TIPS in all patients. Early KU (1-3 min) decreased by more than 55% in two patients who showed a poor prognosis and corresponded well with the status of the portosystemic shunt. It is concluded that 99mTc-GSA hepatic scintigraphy is a useful means of evaluating the degree to which hepatic function is compromised following TIPS. The post-TIPS alterations in HH15, LHL15 and late KU (5-10 min) reflect the changes in hepatic functional reserve, and early KU is a useful index for evaluating the degree of portosystemic shunt. (orig.)

Recently, antimicrobial peptides have been proposed as new agents to distinguish between bacterial infections and sterile inflammatory processes. Based on these considerations, Ubiquicidin peptide 29-41 (UBI) has been labeled with 99mTc using a new direct method showing a radiochemical purity > 97 %, high stability in human serum, and low protein binding. In addition 99mTc-UBI showed a specific in vitro and in vivo binding to bacteria. However its biokinetic parameters have not been evaluated since it is one of the new generation radiopharmaceuticals based on peptide structures. Therefore the aim of this project was to establish the biokinetic model for 99mTc-UBI. An activity from 74 to 148 MBq was injected to patients with bone infection and 5 whole body scans were taken at 1, 30, 120, 240 min and 24 h after radiopharmaceutical administration, with a dual head scanner. Urine was collected for 24 h. An antropomorphic phantom was previously used to calculate the effect of attenuation and scattered radiation on the gamma camera acquisition images. ROIs of the selected organs in patients (kidney, liver, heart, bone, soft tissue and lesion) were drawn, and attenuation and scatter corrected. The % urine elimination at 24 h and time integrated ROIs (cpm/pixel/ROIs) were used to obtain the residence time (τ) in each tissue and to establish the biokinetic model. Pharmacokinetic data show that blood clearance is biexponential with a mean residence time in the central compartment of 0.52 h. The images showed non-accumulation in metabolic organs. More than 75 % of the injected activity was eliminated by renal clearance 4 h after 99mTc-UBI administration. The mean radiation dose calculated according to the MIRD formalism was 0.130 mGy/MBq for kidney and the effective dose was 4.29 x 10-3 mSv/MBq

Recently, antimicrobial peptides have been proposed as new agents to distinguish between bacterial infections and sterile inflammatory processes. Based on these considerations, Ubiquicidin peptide 29-41 (UBI) has been labeled with 99mTc using a new direct method showing a radiochemical purity > 97 %, high stability in human serum, and low protein binding. In addition 99mTc-UBI showed a specific in vitro and in vivo binding to bacteria. However its biokinetic parameters have not been evaluated since it is one of the new generation radiopharmaceuticals based on peptide structures. Therefore the aim of this project was to establish the biokinetic model for 99mTc-UBI. An activity from 74 to 148 MBq was injected to patients with bone infection and 5 whole body scans were taken at 1, 30, 120, 240 min and 24 h after radiopharmaceutical administration, with a dual head scanner. Urine was collected for 24 h. An antropomorphic phantom was previously used to calculate the effect of attenuation and scattered radiation on the gamma camera acquisition images. ROIs of the selected organs in patients (kidney, liver, heart, bone, soft tissue and lesion) were drawn, and attenuation and scatter corrected. The % urine elimination at 24 h and time integrated ROIs (cpm/pixel/ROIs) were used to obtain the residence time (τ) in each tissue and to establish the biokinetic model. Pharmacokinetic data show that blood clearance is biexponential with a mean residence time in the central compartment of 0.52 h. The images showed non-accumulation in metabolic organs. More than 75 % of the injected activity was eliminated by renal clearance 4 h after 99mTc-UBI administration. The mean radiation dose calculated according to the MIRD formalism was 0.130 mGy/MBq for kidney and the effective dose was 4.29 × 10-3 mSv/MBq.

Acute infections, such as appendicitis and occult infections in AIDS patients, can be diagnosed within two hours by gamma scintigraphy after i.v. administration of {sup 99m}Tc labeled antibodies reactive with human granulocytes. The antibody, murine IgM anti-SSEA-1, is partially reduced using Sn(II) to expose and protect reactive sulfide groups. The antibody is then purified, stannous tartrate and stabilizers are added, and the mixture is lyophilized. To label, sodium pertechnetate is added. After a 15 minute incubation the tracer drug is injected. The rate of accumulation and degree of concentration at the site of infection is presumptively determinative of the severity of the infection. Acceptance criteria and tests for the {sup 99m}Tc labeled antibody product have been established and validated. Greater than 93% of the {sup 99m}Tc is firmly bound to the protein as determined by quantitative HPLC. Radiochemical impurities, colloidal {sup 99m}Tc and free pertechnetate are together less than 4% as determined by thin layer chromatography. The immunoreactive fraction, measured by binding to solid phase antigen, and affinity measured be ELISA, are unchanged by the {sup 99m}Tc-direct labeling process. Two hour blood clearance in rats is within 90% of the value of the {sup 125}I labeled analog. The immunoreactive fraction decreases less than 10% when incubated in human plasma for 24 hours. This method has been compared to other direct labeling methods, and found to give higher radiochemical yields. 5 figs.

Overexpression of the multidrug resistance (MDR1) P-glycoprotein (Pgp) has been documented in nearly all forms of human cancers and increased levels of Pgp in some tumors correlate with poor response to treatment. Technetium-99m-sestamibi has recently been validated as a Pgp transport substrate. Pgp is also normally expressed along the biliary canalicular surface of hepatocytes and the luminal side of proximal tubule cells in the kidney, while not expressed in heart. Focused on these organs with known Pgp status, we present the findings on {sup 99m}Tc-sestamibi showed normal, prompt clearance of the radiotracer from the liver and kidneys relative to the heart. After administration of the Pgp modulator, {sup 99m}Tc-sestamibi was selectively retained in the liver and kidneys. Hepatobiliary and renal clearance of {sup 99m}Tc-sestamibi are Pgp-mediated, and inhibition of Pgp transport in these organs can be successfully imaged using {sup 99m}Tc-sestamibi in patients. Similar results might be expected with this and related radiopharmaceuticals for functional imaging of Pgp transport and modulation in tumors. 34 refs., 2 figs.

Several years ago technetium-99m tetrofosmin was reported to localise parathyroid adenomas. The aim of this study was to compare the sensitivity of this radiopharmaceutical with that of {sup 99m}Tc-sestamibi using a double-phase parathyroid scintigraphy protocol. Scans of 12 patients were evaluated visually and lesion to thyroid ratios were calculated. Nine of the patients were subsequently operated on; a total of eight parathyroid adenomas or hyperplastic glands were histologically confirmed in seven of the patients, while in one patient a parathyroid carcinoma was histologically proven. All of these patients had positive {sup 99m}Tc-sestamibi scintigrams, whereas only two {sup 99m}Tc-tetrofosmin scintigrams were positive. With {sup 99m}Tc-sestamibi there was a significant increase in the lesion to thyroid ratio from 10 min to 90 min and 150 min p.i. which was not seen on scintigraphy with {sup 99m}Tc-tetrofosmin. This makes {sup 99m}Tc-tetrofosmin less suitable for double-phase parathyroid scintigraphy. (orig.)

To evaluate availability of cerebral radionuclide imaging for diagnosis of brain death, we examined 25 patients with a suspected clinical diagnosis of brain death. 8 patients were studied by Tc-99m-DTPA and 15 patients were by Tc-99m-HMPAO (Hexamethyl propyleneamine oxime). Seven patients with Tc-99M-DTPA studies revealed absence of cerebral blood flow and sagittal sinus activity. All of 15 patients with Tc-99m-HMPAO studies revealed complete absence of cerebral perfusion. The results of the cerebral radionuclide studies of brain death correlated with other clinical conditions, such as intracranial pressure(ICP), EEG, transcranial doppler sono-graphy(TCDS), and neurologic examination. The ICP of 8 patients, who are confirmed by brain death with Tc-99m-HMPAO study are elevated in all cases. In conclusion, cerebral radionuclide imaging for diagnosis of brain death is available. Tc-99m-HMPAO imaging is unequivocal, easily interpreted, well reflect the physiologic state of increased ICP, and provides adequate assessment of posterior fossa activity. In addition, the SPECT imaging with Tc-99m-HMPAO produces more accurate results due to it's superiority of image contrast and proper localization of radiopharmaceutical distribution than conventional planar imaging.

To evaluate availability of cerebral radionuclide imaging for diagnosis of brain death, we examined 25 patients with a suspected clinical diagnosis of brain death. 8 patients were studied by Tc-99m-DTPA and 15 patients were by Tc-99m-HMPAO (Hexamethyl propyleneamine oxime). Seven patients with Tc-99M-DTPA studies revealed absence of cerebral blood flow and sagittal sinus activity. All of 15 patients with Tc-99m-HMPAO studies revealed complete absence of cerebral perfusion. The results of the cerebral radionuclide studies of brain death correlated with other clinical conditions, such as intracranial pressure(ICP), EEG, transcranial doppler sono-graphy(TCDS), and neurologic examination. The ICP of 8 patients, who are confirmed by brain death with Tc-99m-HMPAO study are elevated in all cases. In conclusion, cerebral radionuclide imaging for diagnosis of brain death is available. Tc-99m-HMPAO imaging is unequivocal, easily interpreted, well reflect the physiologic state of increased ICP, and provides adequate assessment of posterior fossa activity. In addition, the SPECT imaging with Tc-99m-HMPAO produces more accurate results due to it's superiority of image contrast and proper localization of radiopharmaceutical distribution than conventional planar imaging.

Plasma protein binding of Tc-99m was assessed in man after injection of various Tc-99m-labeled bone imaging agents. Of the five methods in which plasma proteins were precipitated to determine protein binding no correlation between them could be established. The ammonium sulfate method seemed to correlate well with dialysis filtration. Plasma obtained from patients injected with Tc-99m phosphate compounds was reinjected to rats. The bone uptake in these animals correlated linearly with the unbound activity in the injected plasma. Provided that no protein binding would occur, the bone uptake as well as the urinary excretion proved to be identical for Tc-99m HEDP, MDP, and PPi. Electrophoresis of Tc-99m PPi indicated that the intact complex may be uncharged, whereas at low ligand concentrations uncharged as well as negatively charged Tc-99m species are formed. Better methods are needed, however, to establish the presence of various Tc-99m species and their relative role in the kinetics of these compounds, and plasma protein binding

Several years ago technetium-99m tetrofosmin was reported to localise parathyroid adenomas. The aim of this study was to compare the sensitivity of this radiopharmaceutical with that of 99mTc-sestamibi using a double-phase parathyroid scintigraphy protocol. Scans of 12 patients were evaluated visually and lesion to thyroid ratios were calculated. Nine of the patients were subsequently operated on; a total of eight parathyroid adenomas or hyperplastic glands were histologically confirmed in seven of the patients, while in one patient a parathyroid carcinoma was histologically proven. All of these patients had positive 99mTc-sestamibi scintigrams, whereas only two 99mTc-tetrofosmin scintigrams were positive. With 99mTc-sestamibi there was a significant increase in the lesion to thyroid ratio from 10 min to 90 min and 150 min p.i. which was not seen on scintigraphy with 99mTc-tetrofosmin. This makes 99mTc-tetrofosmin less suitable for double-phase parathyroid scintigraphy. (orig.)

Metallothionein (MT), a small cysteine-rich protein, was used as a bifunctional chelating agent in the radiolabelling of monoclonal antibodies with Tc-99m. The efficiency of the conjugation reaction of MT with antibodies (Ab) was found as 58%. The yield of radiolabelling of Tc-99m to MT-Ab by reduction method was higher than 90%, while the unspecific radiolabelling occurred less than 10%. The Tc-99m-MT-Ab has proven to be satisfactory stable in Vitro in the presence of a couple of strong chelating agents. The preliminary biological experimental results in tumor-bearing nude mice indicated that the Tc-99m-labelled anti-colorectal carcinoma monoclonal antibody 2C10 had strong affinity toward tumor and was stable in vivo

99mTc-HYNIC-Annexin V was prepared for apoptosis radionuclide imaging in vivo. The expression plasmid of human Annexin V was constructed and expressed in E. coli. HYNIC was prepared and used as bifunctional chelating agent for 99mTc labeling. The radiochemical purity, radiolabeling yield and stability of 99mTc-HYNIC-Annexin V were studied. The coding sequence of human Annexin V gene was successfully cloned into the expression vector, and highly expressed in E. coli. A protein with a molecular weight of about 36kD could be induced and confirmed by Western Blotting and SDS-PAGE. Annexin V could be labeled with 99mTc using HYNIC, and showed high radiochemical purity of more than 90%. The radiolabeling yield could reach more than 90%. The reaction condition was moderate. It suggested that 99nTc-HYNIC-Annexin V may be a promising agent for apoptosis imaging and clinical application.

A 73-year-old patient presented a 99mTc scintiscan with a focal tracer accumulation left and caudal of the thyroid gland. Further investigations with sonography, CT, esophagoscopy and barium swallow provided the diagnosis of achalasia as the reason for focal 99mTc retention caudal of the thyroid gland. Explanation for 99mTc accumulation within the esophagus may be the nonspecific accumulation of 99mTc not only in the thyroid gland but also in the salivary glands. Excretion of the tracer follows with the saliva. Structural and motor disorders of the esophagus can thus lead to focal tracer retention within the esophagus simulating thyroid tissue. PMID:9395425

Development of SPECT imaging agents based on Tc-99m targeting Aβ plaques is useful for diagnosis of Alzheimer's disease (AD). A stilbene derivative, [11C]SB-13, showing promise in detecting senile plaques present in AD patients has been reported previously. Based on the 4(prime)-amino-stilbene core structure we have added substituted groups through which a chelating group, N2S2, was conjugated. We report herein a series of Tc-99m labeled stilbene derivative conjugated with a TcO[N2S2] core. The syntheses of stilbenes containing a N2S2 chelating ligand are achieved by a scheme shown. Lipophilic 99mTc stilbene complexes were successfully prepared and purified through HPLC. Preliminary results of in vitro labeling of brain sections from transgenic mice showed very promising plaque labeling. These 99mTc stilbene derivatives are warranted for further evaluations as potential imaging agents targeting amyloid plaques.

A 73-year-old patient presented a 99mTc scintiscan with a focal tracer accumulation left and caudal of the thyroid gland. Further investigations with sonography, CT, esophagoscopy and barium swallow provided the diagnosis of achalasia as the reason for focal 99mTc retention caudal of the thyroid gland. Explanation for 99mTc accumulation within the esophagus may be the nonspecific accumulation of 99mTc not only in the thyroid gland but also in the salivary glands. Excretion of the tracer follows with the saliva. Structural and motor disorders of the esophagus can thus lead to focal tracer retention within the esophagus simulating thyroid tissue. (orig.)

Technetium-99m glutathione labelled compound is a radiopharmaceutical which is used in nuclear medicine for cancer diagnoses by imaging method. The distribution and accumulation of radiopharmaceutical in the body depend on its physicochemical and biological characteristic. Therefore, the determination of its characteristic was carried out in order to assure the successful utilization of this radiopharmaceutical. The radiochemical purity was determined with thin layer chromatography (TLC-SG) using dried acetone and 0.9% of NaCl solution as a mobile phase. The charge of 99mTc-GSH was tested by electrophoresis method and its lipophilicity (P) was obtained by determination of octanol-water partition. The plasma binding protein of this radiopharmaceutical was in-vitro investigated with precipitation method using 5% of trichloro acetic acid solution. Beside that, studies on the effect of 99mTc radioactivity to the stability of 99mTc-GSH and its stability in plasma has been in-vitro carried out. From the experiment it was obtained that 99mTc-GSH has 99.08 ± 0.26% of radiochemical purity; neutral (no charge); the lipophilicity (P) = 0.03 ± 0.002; the plasma binding protein of 30.31 ± 0.04%. Utilization of 99mTc radioactivity concentration up to 21 mCi/2 mL resulted 99mTc-GSH radiopharmaceutical which was remained stable up to 5 hours with ≥ 95% of radiochemical purity. In-vitro stability test of 99mTc-GSH in plasma indicated that in the first hour of storage, the radiochemical purity drastically decreased and until 5 hours of storage, its radiochemical purity did not change significantly, that was about 50%. (author)

Hypodermic injection of technetium-99m (99mTC-pertechnetate) at points of low electrical resistance give rise to rapid, longitudinal, and progressive diffusion of the radioactive tracer. We assessed the effect of cutaneous incisions that did not intersect the migration trajectory of 99mTc-pertechnetate and the re-establishment of pathways after the suture of incisions that intersected the migration trajectory. Linear and rapid migration of 99mTc-pertechnetate was not altered or prevented by incisions that did not intersect the migration pathway. Different patterns of 99mTc-pertechnetate spread were found when incisions intersected the radioactive pathways until restoration of the normal migration pathway observed in undamaged skin occurred. In all experiments in which migration of 99mTc-pertechnetate was observed, lavage of surgical wounds was followed by disappearance of the 99mTc-pertechnetate migration observed around the suture. Linear migration of the tracer was not observed when the incision was left uncovered, filled with petroleum jelly, or with a solid silicone sheet, but it was seen when non-sutured incisions were filled with transonic or silicone gel or covered with a solid silicone sheet parallel to the cutaneous plane. These data show that after a cutaneous incision that intersected the diffusion trajectory of the radioactive tracer, linear migration of 99mTc-pertechnetate hypodermically injected at points of low electrical resistance was restored before healing of the cutaneous incision and was independent of incisions made on the skin not overlying the radioactive pathway. A mechanism similar to that of capillary electrophoresis is suggested to explain the hypodermic diffusion of inert particles through specific and constant linear pathways. (orig.)

The syntheses of four α-aminomethyl phosphonates and their complexation studies with 99mTc and 186/188Re are reported. Complexation conditions were standardized to give maximum yields, which ranged from 90-97%. The yields of complexation were estimated by paper chromatography. The 99mTc complexes were stable for more than 4 h, while the 186/188Re complexes were stable for 3-8 days when stored at 4 deg. C. Biodistribution of these complexes in Wistar rats were carried out, and the uptake in bone and other soft tissue are detailed. Bone uptake of the 99mTc complexes varied from 40-60% at 30 min postinjection depending on the ligands. The uptake in soft tissue was minimum with all the complexes. A comparison of the biodistribution studies of the 99mTc complexes with that of the well-established radiopharmaceutical 99mTc-MDP was carried out for the purpose of evaluating the efficacy of the radiopharmaceutical preparation with the complexes of these ligands. The bone uptake of the 186/188Re complexes varied from 19-28% corresponding to 1.6-3% per g at 3 h postinjection. The residual activity in both 99mTc and 186/188Re complexes showed renal clearance

The labelling of red blood cells (RBC) with technetium 99m (99m Tc) depends on several factors, as the stannous ion (Sn++) concentration, the time and temperature of incubation, the anticoagulant utilized, the presence of plasma proteins (PP) and others. Although the blinding of 99m Tc with hemoglobin and PP are similar, they appear to have specific characteristics as demonstrated by precipitation with alcohol, acetone, trichloroacetic acid, hydrochloric acid and mercury chloride. The bacterial cultures labeled with Technetium-99m, at optimal Sn++ ion concentration, presents a large stability and their viability is not altered by this treatment. The electrophoretic mobility, the hydrophobicity, the cationized ferritin distribution and the adherence to human buccal epithelial cells are not modified either. The possibility of labelling with 99m Tc of planaria and cercariae of Schistossoma mansoni evaluative cycle increases the utilization of this radionuclide to an experimental level. The results described with the labelling of these biological structures with 99m Tc demonstrated that stable labeled and viable operations are obtained. (author)

Dextran-70 labelled with 99m Tc is used for lymphocintigraphy in Nuclear Medicine. The aims of this work were: the lyophilized kit formulation; the radiochemical quality control determination and the biodistribution studies in Wistar rats. Each lyophilized vial contains: 50 mg Dextran-70 (Sigma); 750 μg Sn Cl2. 2 H2 O, pH = 4.0. For the radiochemical determination the following parameters were assayed: Chromatography systems (Whatman 3MM, TLC-SG (Silica-gel) e TLC-A1 (aluminium); the 99m Tc activities (37, 111 and 1850 MBq); the 99m Tc volumes (1,3,5 and 8 mL) and the stability after the lyophilization process (1, 3, 6, 12 and 24 months). The Whatman 3MM chromatography system using acetone as solvent presented a purity yield of 99.88; 99.70; 99.00 and 98.92% using 1, 3, 5 and 8 mL of 99m Tc, respectively. The yield of labelling showed 99.80 % of radiochemical purity using 1850 MBq of 99m Tc, after 24 months. The biological studies were performed in Wistar rats, average weight 250g, after intravenous administration of 99m Tc-Dextran-70 (2.96 MBq). A slow blood decrease with high hepatic uptake was mesured. The high kidney uptake observed, during the experiment, was due the experiment, was due the fact that the animals were kept under anaesthesic effect. (author). 4 refs., 2 figs., 4 tabs

Sixteen patients with soft tissue malignancy or fibroadenoma of the breast (Group A) were imaged using 99mTc-citrate. Majority of the patients (n=14) has new untreated lesions. Appreciable skeletal uptake of the tracer was serendipitously noticed in all cases. One of these had widespread bone metastases seen almost identically in 99mTc-citrate and 99mTc-MDP studies. Accordingly, 10 patients (Group B) having more than 40 malignant lesions on the bone scan underwent 99mTc-citrate study. In group A, accumulation of the tracer was seen in all malignant breast nodules and axillary lymphnode mass (n=4), medullary carcinoma of the thyroid along with its metastasis and a carcinoid (n=4) and an ovarian malignancy. Uptake and outflow pattern could differentiate fibroadenoma (n=3) from carcinoma of the breast. No significant uptake was seen in liver secondaries (n>10), lymphoma lesions (n=5), papillary carcinoma of thyroid, renal cell and embryonal cell carcinoma. In group B patients, the radiotracer accumulated well in the metastatic lesions while there was distinctly lesser uptake in normal/degenerated joints compared to the bone scan. The study shows potential of the tracer in imaging soft tissue malignancies. Bone scanning with 99mTc-citrate is an interesting possibility since mechanism of its uptake appears to be different to 99mTc-MDP. (author)

The authors performed scintigraphy using 99mTc(V)-DMSA (Technetium-99m pentavalent dimercaptosuccinic acid) on patients with pituitary adenomas. Three non-functioning (100%), 2 GH-secreting (67%), 4 PRL-secreting (80%), and zero ACTH-secreting (0%) adenomas concentrated the 99mTc(V)-DMSA, but all 5 of the non-adenomatous lesions and 1 normal pituitary gland did not. There was no significant relationship between tumor-to-background ratios and tumor sizes, or the serum hormone level. The 99mTc(V)-DMSA scintigraphy showed an overall sensitivity of 69% (9/13) in detecting pituitary adenomas, which increased to 82% for non-functioning, GH-secreting and PRL-secreting adenomas. In conclusions, 99mTc(V)-DMSA was found to be a suitable radiotracer for detecting pituitary adenomas. But further studies are necessary to define the processes that concentrate 99mTc(V)-DMSA and their role in pituitary adenomas. (author)

Full text. Metabolic models describe organisms as compartments. An organ or tissue may be constituted of one or more compartments, from where a tracer (T) is eliminated or transferred to other organs. A compartmental model must follow the metabolic of T and still be simple enough to allow easy interpretation of results. 99m T C-M D P is largely used in nuclear medicine routine for bone scintigraphy (B S). The objective of this work is to evaluate the biokinetic model of 99m Tc-M D P (which is eliminated by the urinary tract) in patients (pts) of both sexes submitted to routine B S. Urine samples of 10 pts were collected at different times of incorporation for 'in vitro' measurements, which were performed by means of a collimated Nal-Tl crystal counter, calibrated with a standard solution. Pts suffering from systemic bone disease were not included in this study. The results obtained are presented as specific activity/time curves 39-75 pts 16-18 years and a 16 month old child. All curves are characterized by two terms: a faster one and a slower one.A very fast initial term, which is present in the first half hour cannot be easily seen in the curves because data were not appropriately collected. such measurements will be done 'in vivo'. The shape of all curves indicate that it is possible to establish normality patterns for 99mTc-MDP metabolism

Conjugates of For-MLFK and For-NleLFNleYK with S-benzyl mercaptoacetyl dipeptides containing, respectively, zero, one, and two carboxyl functions in their structures were prepared and labeled with {sup 99m}Tc. In vitro binding studies using isolated human granulocytes indicated specific receptor binding of the radiolabeled conjugates. The fraction of granulocyte-associated activity was determined after incubation with total blood. Biodistribution studies of the {sup 99m}Tc-peptides in normal mice revealed a very fast blood clearance proceeding mainly via the hepatobiliary system. Urinary excretion was higher for conjugates containing carboxyl functions in their ligand structures.

N,N-bis-(1-carboxy-2-mercaptoethyl)ethylenediamine(EC), a precursor for potential new generation technetium radiopharmaceutical for renal function studies, was synthesized in simple two step method. High percentage labelling (90%) was achieved during its radiopharmaceutical preparation with Tc-99m pertechnetate in presence of stannous chloride. Its renal clearance in experimental animals was found to be better than that of 131 I-ortho-iodohippuric acid and comparable to that of the recently developed 99m Tc-MAG3. 13 refs., 7 tables (author)

Kinetic parameters of sup(99m)Tc and 131I thyroid trapping were compared in 13 patients (28 dynamic studies). The data were analyzed with a six-compartment model including three compartments for extrathyroid spaces. There was a good correlation between the estimates of the total iodide and pertechnetate pools (V4+V5). As expected, the lambda14 loss rate constant for technetium was always higher than that for iodide. In five euthyroid patients, the unidirectional clearances (R41) with TcO4- and I- were generally of the same magnitude. The effect of TSH stimulation appears to be identical for both isotopes: an increase of R41 and the total iodide and pertechnetate pool (V4+V5), a decrease of the isotope loss rate constant (lambda14). In two untreated thyrotoxic patients, the unidirectional clearance of sup(99m)Tc was 2.5 times higher than that estimated with 131I. Under administration of antithyroid drug, unidirectional TcO4- clearance was lower than that of iodide in the six patients studied. A similar and greater discrepancy between early 131I and sup(99m)Tc kinetics was observed in a patient with congenital goiter. The technetium thyroid trap was only slightly elevated, whereas unidirectional iodide clearance and (V5+V5) were clearly increased. This series of patients suggests that whereas there is a good correlation between early 131I and sup(99m)Tc kinetics in euthyroid subjects, a discrepancy exists in patients with spontaneous or acquired dyshormonogenesis. This is confirmed by the segmentary study of a patient with a nodule appearing hot on the sup(99m)Tc scintigram and cold on the 131I scan. (orig.)

A simple kit with a lyophilized preparation of sup(99m)Tc-labeled dimercaptosuccinate is described. The kit consistently provides more than 80% yields of the complex having kidney seeking properties. The distribution of the complex was observed in humans by blood clearance, external renal measurements and scintillation camera imaging. Radiation dose based on distribution in human organs was calculated. The dose for whole body, kidney, testes and ovaries was 18.7 mrad/mCi, 674 mrad/mCi, 14.5 mrad/mCi and 20.6 mrad/mCi, respectively. (auth.)

The oral administration of proteic antigens, like ovalbumin, may result in the induction of oral tolerance or immunization. The aim of this work was to label a protein antigen with 99m Technetium, encapsulate it in liposomes and investigate its absorption and tissue distribution after oral administration in mice. Ovalbumin was labeled with 99mTechnetium and encapsulated in small unilamellar vesicles. 99mTc-OVA encapsulated or not in liposomes was administrated to mice that were sacrificed after different times. The radioactivity was measured in various organs of the animals. Differences concerning the biodistribution of 99mTc-OVA were noticed. The technique may represent alternatives for the induction of immunization or oral tolerance.(author)

Kanamycin and gentamicin are aminoglycosides antibiotics indispensable in the therapy of acute infections. Labelling with Tc-99m depends on the ligand and reducing agent concentrations, pH and the reaction time. Radiochemical yield and stability were determined by paper and thin layer chromatography. Biodistribution studies of 99mTc-kanamycin and 99mTc-gentamicin were performed in rats. The localization of radioactivity of both complexes in infected sites induced by Staphylococcus aureus indicated the high binding affinity of these drugs. 99mTc-gentamicin has an effective bacterial action against gram positive bacteria S. aureus which confirms the efficacy of this complex as diagnostic agent for bacterial infections.

Tc-99m dimercaptosuccinic acid (DMSA) is filtered through the glomeruli and reabsorbed by the proximal tubules as low molecular weight proteins. In Lowe syndrome this mechanism is impaired and so poor DMSA uptake is seen. Poor DMSA uptake was shown in very few studies, but none mentioned normal Tc-99m MAG3 uptake. In this case, the patient had poor DMSA uptake, normal MAG3 uptake and a neurogenic bladder in anterior to the left kidney that attenuates left kidney.

Radiopharmaceuticals are compounds, with no pharmacological action, which have a radioisotope in their composition and are used in Nuclear Medicine for diagnosis and therapy of several diseases. In this work, the development and validation of an analytical method for 99mTc-HSA, 99mTc-EC, 99mTc-ECD and 99mTc-Sestamibi radiopharmaceuticals and for some raw materials were carried out by high performance liquid chromatography (HPLC). The analyses were performed in a Shimadzu HPLC equipment, LC-20AT Prominence model. Some impurities were identified by the addition of a reference standard substance. Validation of the method was carried out according to the criteria defined in RE n. 899/2003 of the National Sanitary Agency (ANVISA). The results for robustness of the method showed that it is necessary to control flow rate conditions, sample volume, pH of the mobile phase and temperature of the oven. The analytical curves were linear in the concentration ranges, with linear correlation coefficients (r2) above 0.9995. The results for precision, accuracy and recovery showed values in the range of 0.07-4.78%, 95.38-106.50% and 94.40-100.95%, respectively. The detection limits and quantification limits varied from 0.27 to 5.77 μg mL-1 and 0.90 to 19.23 μg mL-1, respectively. The values for HAS, EC, ECD and MIBI in the lyophilized reagents were 8.95; 0.485; 0.986 and 0.974 mg L-1, respectively. The mean radiochemical purity for 99mTc-HSA, 99mTc-EC, 99mTc-ECD and 99mTc-Sestamibi was (97.28 ± 0.09)%, (98.96 ± 0.03)%, (98.96 ± 0.03)% and (98.07 ± 0.01)%, respectively. All the parameters recommended by ANVISA were evaluated and the results are below the established limits. (author)

Several methods have been developed to label antibodies with 99mTc. Direct labeling results in 99mTc binding to multiple sites of various affinities that are often weaker than the binding to strong chelating agents. Attempts to overcome this disadvantage involve conjugation of strong chelating agents to the antibodies. While stability is usually enhanced, this approach suffers from alteration of antibody properties as well as non-specific binding of 99mTc to the antibody instead of to the conjugation chelating agent. This has been of concern for studies with DTPA as the chelating agent. In this study the loss of 99mTc by N2S2 challenge shows that a fraction to the 99mTc is nonspecifically bound to the antibody. An advantage of the approach of labeling antibodies containing a bifunctional chelating agent is the simplicity of the labeling procedure and the apparent high yields that in reality are the sum of chelating agent and non-specifically bound radioactivity. The last approach described in our work of conjugation of a preformed chelate has advantages of characterizable 99mTc complex chemistry and conjugation by standard protein derivatization chemistry. Slow chelation kinetics can be overcome in the small molecule stage and then conjugation performed under mild conditions with respect to the antibody of fragments. This approach, however, suffers from greater complexity of the labeling process including multiple steps, purifications and non-quantitative yields. The use of ligands for 99mTc in which the complexes are of high stability and predictable chemistry is likely to result in eventual optimal labeling technologies. Processes which are non-specific may work in some cases, but are likely to present difficulties in optimization and general applicability from antibody to antibody. (orig.)

For several years, radioaerosols have been successfully used to provide detailed images of regional ventilation to aid in the differential diagnosis of pulmonary embolism. It has been widely advocated that the ventilation images should follow the perfusion scan and that the amount of aerosol deposited in the patient's lungs should be three times greater than the perfusion dose. We employed an alternative approach which avoided the deposition of an unpredictable amount of aerosol in individual patients. The aerosol study was performed first, and the activity of the microspheres used for the perfusion images was then tailored to the actual amount of aerosol which the patient had retained. This allowed a microsphere/aerosol activity ratio of 10:1 to be readily achieved, thus successfully masking the ventilation pattern by the perfusion activity. The faster biological clearance of sup(99m)Tc-DTPA aerosol from the lung fields, as compared to sup(99m)Tc-sulphur-colloid aerosol, allowed higher initial activities to be deposited in the lungs, thus enabling a high-resolution collimator to be used. When the perfusion study was delayed by 1 h (one effective half-life for the sup(99m)Tc-DTPA aerosol), it was not necessary to increase the perfusion activity required to mask the ventilation image. (orig.)

[sup 99m]Tc-DTPA-galactosyl human serum albumin ([sup 99m]Tc-GSA) is a new liver-imaging agent which binds to hepatic binding protein. This study evaluated the sensitivity of [sup 99m]Tc-GSA kinetics and imaging anatomy to hepatic ischemia-reperfusion injury of obstructive jaundiced rats. Regional hepatic ischemia was induced by clamping the left hepatic artery and the left portal vein for 45 min. The blood clearance and hepatic accumulation indices were obtained on the basis of the dynamic data. A significant difference of these indices was observed between the ischemic group and the control. Marked depression in hepatic [sup 99m]Tc-GSA uptake was observed in the ischemic group. In conclusion, [sup 99m]tc-GSA is useful for evaluating the hepatic ischemia reperfusion injury in rats with obstructive jaundice. (author).

A technetium-99m-labeled peptide derived from ubiquicidine, further referred to as 99mTc-UBI 29-41, targets bacterial and fungal infections, but not sterile inflammatory processes, in experimental animals. This paper reports on the radiochemical and biological features of this radioactive agent and the importance of the amino acid sequence of UBI 29-41 for imaging of infections. Radiochemical analyses of 99mTc-UBI 29-41 and a radiolabeled scrambled version of this peptide, i.e. 99mTc-Sc-UBI 29-41, revealed that both peptides were labeled rapidly (within 10 min) and effectively with little colloid formation (less than 5% of the total radioactivity) and very little free pertechnetate (or radioactive intermediates) in the preparations containing radiolabeled peptide. Furthermore, association of the peptides with bacteria could be competed with excess unlabeled peptide and this association proved to be temperature-dependent. Based on this in vitro data we concluded that labeling of peptides with 99mTc by this direct method is rapid, efficient, and safe. Scintigraphy demonstrated that radioactivity is rapidly removed from the circulation (half-lifes of UBI 29-41 and Sc-UBI 29-41 were 16 and 21 min, respectively) mainly by renal clearance. Analysis of murine blood revealed that only a small proportion of the intravenously injected 99mTc-peptides is associated with blood cells. Although both radiolabeled peptides accumulated rapidly at sites of infection, the values for 99mTc-UBI 29-41 were higher (P 99mTc-Sc-UBI 29-41. Moreover, injection of excess unlabeled UBI 29-41, but not Sc-UBI 29-41, into Staphylococcus aureus-infected mice prior to injection of 99mTc-UBI 29-41 significantly (P99mTc-UBI 29-41 at the site of infection in mice using a carrier-free radiolabeled UBI 29-41 as compared with unpurified preparations containing radiolabeled UBI 29-41. This in vivo data indicates that the amino acid sequence of 99mTc-UBI 29-41 contributes to its accumulation at the site of

Preparation of 99mTc-labelled tetrapeptides, namely acetyl-Gly-Gly-Cys-Gly (I), acetyl-Ser-Ser-Cys-Gly (II) and acetyl-Gly-Gly-Cys-Lys (III), analysis of their radiochemical purity and biodistribution were investigated in rats. The aim was to determine the relationship between structure and biological behaviour of 99mTc-labelled peptides which are formed by amino-acid sequences capable of chelating technetium useful as universal chelators in ''hybrid'' peptides composed of receptor-specific part and the part chelating technetium. For labelling with 99mTc, a conventional transchelation from 99mTc-gluconate was used and radiolabelled peptides were purified by filtration on Whatman microfilters 12 kD. Radiochemical purity was higher than 98%. Biodistribution studies in rats showed that all agents are rapidly cleared from the body mostly via urine, but some part of administered radioactivity also in the faces was found. The later route of elimination way increased in the order III99mTc-MAG3. The results obtained will assist with design of optimal biocompatible tetrapeptides as chelators for formation of hybrid receptor-specific peptides. (author)

Nuclear medicine is a medical specialty which uses radioactive compounds (radionuclides) for diagnostic and therapeutic purposes. 99m Tc is the more common radionuclide used in many studies in nuclear medicine because its advantages: it has a photopeak of 140 KeV and a half-life of 6 hours; it can be eluted from a Molybdenum 99 generator, so radiopharmaceuticals can be prepared on site. Ethyl cysteine dimer (ECD) labelled with reduced Technetium 99m has been purposed recently as a promising radiopharmaceutical for brain perfusion imaging 99m Tc-ECD is a lipophilic neutral complex which cross the brain blood barrier and show high brain uptake. The objective of this work was synthesize and to design a freeze dried formulation for the instant preparation of 99m Tc-ECD complex useful for brain perfusion imaging. We obtained a freeze dried stable formulation for the preparation of 99m Tc-ECD kit with a radiochemical purity higher than 90 %, which fulfills with the quality control of radiopharmaceuticals. Furthermore, we developed analytic techniques for the determination of the different chemical compounds into the lyophilized kit. (Author)

The purpose of the study is to analyze the regional renal dynamic process (renal perfusion, accumulation and clearance) using Tc-99m DTPA and assess for the regional renal indices from this analysis early to detect acute tubular necrosis and acute rejection of post transplant kidneys. The subjects were 6 normal donors and 10 post renal transplant patients. Tc-99m DTPA (20 mCi) was injected into the vein by a bolus, and its activity change in the kidney was measured by a scintillation camera, and stored each 1 sec. for 20 sec. following each 15 sec. for 20 min. in the computer, to calculate the renal functional indices: the perfusion index, the blood flow mean transit time, the accumulation rate and the clearance rate in the cortex, medulla and pelvis, whose R.O.I. regions were separated in the early and late scinti-images. The accumulation ratio, a new parameter, which is the second upslope part of Tc-99m DTPA renogram, and the clearance rate were calculated from H/A method. The authors made the functional images of these indices to estimate their regional distribution. The accumulation rate and the clearance rate only in the cortex were markedly decreased in the acute tubular necrosis and the rejection, which functional images showed irregular distributions. It was possible to evaluate the renal perfusion with Tc-99m DTPA, separated from the renal accumulation and clearance process. The authors' method gave the assessment of the regional renal disorders with the functional images; the renal disorders in acute tubular necrosis and acute rejection exist mainly in the cortex

Nine maxillary sinuses of 8 patients who had undergone Caldwell-Luc surgery (CWL) were injected with 100-125 μC 99mTc-DTPA in 0.2 ml from the gingivo-buccal sulcus, passing through the canine fossa window. Sinus half-emptying times and percent contribution of the natural ostium (NO) and the naso-antral window (NA) to the clearance from the sinus were calculated, using time-activity curves as well as the activity of cotton wool plugs placed into the middle and lower conchae. Mean half-emptying times in patients in whom the mucosa had been removed were shorter than those in patients in whom it had been left in place. In the former group percent drainage through the NO was higher than that through the NA whereas in the latter group the opposite was the case. These findings are consistent with the thesis that if the mucosa is retained, the ciliae continue their sweeping action towards the NO but if it is removed the NA gains importance in the drainage. This method is promising for the evaluation of maxillary sinus drainage following CWL. (orig.)

Mesalamine was labelled with technetium-99m (99mTc) in high radiolabelling yield (∼98.4 %), in vitro stability (∼4 h) and in serum persistence (∼24 h). Optimum labelling conditions were investigated. The structure of the complex was confirmed using in silico analysis. Molecular docking was performed to evaluate the complex binding to its biochemical target, the PPARc receptor. Biodistribution and clearance studies were performed in normal and ulcerative colitis models in mice. The tracer's localization was highest (∼65.2 %) in microbial model compared to chemical model (∼42.4 %) and normal mice (∼22.1 %) at 60 min post injection. All data supported the usefulness of 99mTc-mesalamine as a radiotracer for ulcerative colitis. (author)

The use of radiotracers in research of animal venom has been scarce, although it allows an excellent approach to follow the process of biodistribution and kinetics of toxins, and tissue distribution studies are very important for clinical use. Our group has demonstrated that Scorpaena plumieri venom (SP) possess high antitumoral activity and can be a source of template molecules for the development of antitumoral drugs. The purpose of this study was to radiolabel SP with 99mTc and investigate its biodistribution profile. High labeling yield was obtained and the results suggest that [99mTc]SP can be an useful tool for in vivo studies. The analysis indicated that SP is excreted manly by the kidneys with a slow clearance rate. The significant [99mTc]SP uptake in the heart and lungs may explain, at least partially, the pulmonary edema and effect cardiac observed by the envenoming. (author)

To evaluate the hepatic functional reserve, 99mTc-GSA liver scintigraphy was applied for 31 children with various liver diseases (biliary atresia in 7, liver dysfunction of unknown origin in 6, chronic hepatitis in 5, congenital biliary dilatation in 3, neonatal hepatitis in 2, and others in 8). Their ages ranged from 27 days to 15-year-old. A liver biopsy was also taken for pathology in 20 of them. The time when cumulative radioactivity of the liver reached 85% of the heart plus liver radioactivity was determined as T0.85. The patients were divided into three groups based on T0.85 as follows: group I (n=19), T0.850.850.85≥10 min. Receptor index (LHL15) and T0.85 showed correlations with cholinesterase, serum albumin, and hepaplastin testing. The clearance index (HH15) also had correlations with prothrombin time and cholinesterase. Each indicator got worse in accordance with the severity of histological inflammation and fibrosis. There was a significant correlation between T0.85 and HH15 as well as between T0.85, and LHL15. Four cases out of 14 in group III were candidates of liver transplantation. This result corraborates the usefulness of HH15, LHL15 and T0.85, calculated by 99mTc-GSA liver scintigraphy, in evaluating the hepatic functional reserve in children with various liver diseases. (author)

A noninvasive method for measurement of the individual kidney filtration fraction (FF) is presented, based on an analysis of the early rise of the kidneys' time-activity curves obtained after simultaneous injection of tubular (/sup 131/I) ortho-iodohippurate and glomerular (Tc-99m DTPA) tracers. The analysis is based on the assumption that an insignificant amount of tracer leaves the kidney during the first few moments following injection. Therefore the kidney activity during this period is directly proportional to the integral of the blood (heart) activity. The dual-tracer technique allows the direct calculation of the ratio of glomerular to tubular clearances, i.e., the FF. In vivo studies were performed on 12 dogs, including normals as well as others with acute ureteral ligation or Benemid-induced tubular blockade. The calculated FF correlated well with the FF obtained from single-shot clearances performed simultaneously. We conclude that the FF can be calculated directly for each kidney, noninvasively, from the early part of the tubular and glomerular time-activity curves by noninvasive external detection.

Practical description is given of equipment and operations necessary in the preparation of an isotopic generator of technetium-99m. The preparation and application of the active solution and throughly washed of the chromatographic column have been studied in order to allow molibdenum-99 to be adsorbed on a small band, and the solution of tectium-99m to be eluted with high efficiency and purity. The equipment and accesories used are easy and safety to manage, simplifying operations to be carried out with the active product, eliminating the sterile environment in the shielded cell, and facilitating the preparation of the solution of technetium-99m in sterile and pyrogen-free conditions.(author)

This invention concerns a new peptide labelled with sup(99m)Tc. It also covers the process for preparing this labelled peptide as well as the therapeutical mixture containing it in conjunction with a physiologically acceptable excipient. One of the purpose of the invention is to suggest a new vector providing a faster localization of the sup(99m)Tc, particularly with respect to the pituitary gland and the other organs so that the 99m isotope of the technetium reaches the organs to be visualized in under 10 minutes and so that the total administering and recording time by means of a scintillation camera connected to a computer and a fast printer is not more than 20 minutes. The invention was achieved through the choice of a particular peptide that is found in the amino-acid sequences of natural hormones (ACTH, MSH)

Preparation of '9'9'mTc-Ciprofloxacin for diagnosis of bacterial infection was investigated in this research. Factors including pH, injected dose and the purity of 99mTc-Ciprofloxacin were determined. The optimal labeling condition of 99mTc-Ciprofloxacin was found to be at pH 4.0-5.0. In terms of efficiency, the injected dose per gram of infected area was 0.25-0.56, which lasted for the duration of 1-3 h after injection. The radiochemical purity remained >90% with stability for the duration of 6 h. Therefore, this study has demonstrated the preparation of sterile, pyrogen-free and non-toxic 99mTc-Ciprofloxacin.

Leukocyte labelling with Tc-99m may result in a useful method for the detection and localization of active inflammatory processes in patients, particularly in the pediatric population. Previous studies qin this laboratory have shown that hexakis(alkylisonitrile)technetium(I) complexes readily label V79 lung fibroblasts in vitro, and this work is now being extended to isolated human white blood cells (WBC). Two lipophilic water-soluble technetium cations, the t-butyl [Tc-99m(TBI)] and cyclohexyl [Tc-99m(CHI)] analogs, were prepared essentially ligand-free at no-carrier-added levels in aqueous media and introduced in 10% propylene glycol/90% normal saline solution to WBC at room temperature. The cells were isolated from whole blood via sedimentation, centrifugation, and hypotonic hemolysis of the red blood cells. The labeling yield was studied as a function of incubation time (10-45 min), amount of activity (0.35-8.0 mCi), and total WBC (2.5 x 10/sup 7/-1.3 x 10/sup 8/). After 10 min incubation using 10/sup 8/ cells, the initial uptake of Tc-99m(TBI) was 40%, of which 50% remained bound after one saline wash. By contrast, the labeling efficiency with Tc-99m(CHI) was 85%, with 90% of the label still bound after washing. The labeling yield was unrelated to activity levels of incubation time, but was proportional to the number of WBC present. The entire process could be complemented in approximately one hour. The labeling yields with Tc-99m-(CHI) are comparable to those now obtained with the clinically available In-111 oxine

The cationic complex Tc-99m t-butylisonitrile (TBI) concentrates in the myocardial tissue of several animal species. Its myocardial distribution is proportional to blood flow both in zones of ischemia and in normal myocardium at rest. Planar, tomographic, and gated myocardial images have been obtained using Tc-99m TBI in the human. The authors investigated the potential application of Tc-99m TBI imaging to detect and localize myocardial infarction. Four subjects without clinical evidence of cardiovascular disease and five patients with ECG evidence of previous myocardial infarction were studied. Tc-99m TBI (10mCi) was injected intravenously with the patient in a resting state with planar imaging in the anterior, 30 and 70 degree LAO projections beginning one hr after injection. The distribution of the tracer was homogeneous throughout the left ventricular wall in the normal subjects. Regional perfusion defects were present in 4/5 of the patients with myocardial infarction. Location of the defects corresponded to the location of the infarct using ECG criteria (2 inferoposterior and 2 anterior). The patient in whom the Tc-99m TBI image appeared normal had sustained a subendocardial myocardial infarct which could not be localized by ECG; the other 4 pts had transmural infarcts. Anterior and 30 degree LAO images were of excellent quality in all cases; there was overlap of the liver on the inferior wall of the left ventricle on the 70 degree LAO views. The authors conclude that accurate perfusion imaging may be possible using Tc-99m TBI in patients with transmural myocardial infarction

The cationic complex Tc-99m t-butylisonitrile (TBI) concentrates in the myocardial tissue of several animal species. Its myocardial distribution is proportional to blood flow both in zones of ischemia and in normal myocardium at rest. Planar, tomographic, and gated myocardial images have been obtained using Tc-99m TBI in the human. The authors investigated the potential application of Tc-99m TBI imaging to detect and localize myocardial infarction. Four subjects without clinical evidence of cardiovascular disease and five patients with ECG evidence of previous myocardial infarction were studied. Tc-99m TBI (10mCi) was injected intravenously with the patient in a resting state with planar imaging in the anterior, 30 and 70 degree LAO projections beginning one hr after injection. The distribution of the tracer was homogeneous throughout the left ventricular wall in the normal subjects. Regional perfusion defects were present in 4/5 of the patients with myocardial infarction. Location of the defects corresponded to the location of the infarct using ECG criteria (2 inferoposterior and 2 anterior). The patient in whom the Tc-99m TBI image appeared normal had sustained a subendocardial myocardial infarct which could not be localized by ECG; the other 4 pts had transmural infarcts. Anterior and 30 degree LAO images were of excellent quality in all cases; there was overlap of the liver on the inferior wall of the left ventricle on the 70 degree LAO views. The authors conclude that accurate perfusion imaging may be possible using Tc-99m TBI in patients with transmural myocardial infarction.

Transferrin receptors (Tf-R) were expressed on the surfaces of cancer cells. In cancer cells that are rapidly proliferating, transferrin receptors are upregulated due to the need for increasing non-hem iron to catalyze the first and rate-limiting step of DNA synthesis. Therefore transferrin (Tf) is thought to be a major ligand to find cancer cells. In this study, we investigated the targetability of Tf conjugated compounds to Tf-R expressed on cancer cells for detection and diagnosis and the usefulness of gamma probe-targeting delivery system on monitoring whether the gene complex bind to the cells specifically. For the detection and diagnosis of Tf-R positive cancer cells, Tf-chitosan conjugates were synthesized as previously described by Kircheis et al with some modifications. Succinimidyl 6-hydrazino nicotinate hydrochloride (HYNIC) was bound to Tf-chitosan conjugates. HYNlC-Tf-chitosan conjugates were labelled with 99m Tc. For tumor model, 5- to 6-week-old female BALB/c nude mice were injected subcutaneously in the left thigh with Ramos cells (human Burkitt's lymphoma). The gamma imagings were acquired after administration of Tc-99m Tf-chitosan conjugates. To compare the image acquired with HYNIC-Tf conjugate, Ga-67 study was performed. Radiolabeling yields of both Tf-chitosan conjugates was above 90% until 12hr. Uptake in the Ramos model of Tc-99m Tf-chitosan conjugate showed higher than those of Ga-67. A few minutes after injection Tc-99m Tf-chitosan conjugate localized mainly in the circulation (heart), kidneys, and tumor. At 24hr after injection, tumor to nontumor ratio of Ga-67 was approximately 4, but those of Tc-99m Tf-chitosan conjugate showed until 5 only 2 hr after injection. Using Tc-99m Tf-chitosan conjugate, transferrin binding to transferrin receptor on tumor cell could be seen in vivo.

Lee, Kang Wook; Lee, Heon Young [Chungnam National University College of Medicine, Daejeon (Korea, Republic of)

1995-06-15

Reflux of bile and digestive enzymes from the small bowel and duodenum into stomach has been observed in patients with various gastroduodenal diseases. Tc-99m iminodiacetic acid derivatives hepatobiliary scan has been used as a noninvasive method to detect duodenogastric reflux. Sometimes, gastric reflux can be observed incidentally on routine Tc-99m DISA hepatobiliary scintigraphy. To evaluate the clinical meaning of gastric reflux on routine Tc-99m DISIDA hepatobiliary scan, we analyzed 36 patients showed gastric reflux incidentally on the routine Tc-99m-DISIDA hepatobiliary scintigraphy from December 1991 to June 1995 in Chungnam National University Hospital. The results were as follows: 1) The gastric reflux was observed in 2.3% of 1,553 cases of routine Tc-99m DISIDA Hepatobiliary scintigraphy for 43 months. 2) Nineteen percent of patients with gastric reflux had the past medical history of operations on stomach or biliary system. And that history was more prevalent in patients with reflux than those without reflux, significantly (p<0.01). 3) On fiberoptic gastroduodenpscopic examination, 87% of the patients with gastric reflux had the gastroduodenal diseases such as gastritis, gastric ulcer, duodenal ulcer, gastric cancer, duodenal cancer and ampullary diverticulosis. We thought that the gastric reflux can be observed considerably in patients without any operation history on stomach or duodenum, although the operation history is more prevalent in patients with gastric reflux than those without reflux, significantly and most of patients with gastric reflux on routine Tc-99m DISIDA scan has various gastroduodenal diseases.

Reflux of bile and digestive enzymes from the small bowel and duodenum into stomach has been observed in patients with various gastroduodenal diseases. Tc-99m iminodiacetic acid derivatives hepatobiliary scan has been used as a noninvasive method to detect duodenogastric reflux. Sometimes, gastric reflux can be observed incidentally on routine Tc-99m DISA hepatobiliary scintigraphy. To evaluate the clinical meaning of gastric reflux on routine Tc-99m DISIDA hepatobiliary scan, we analyzed 36 patients showed gastric reflux incidentally on the routine Tc-99m-DISIDA hepatobiliary scintigraphy from December 1991 to June 1995 in Chungnam National University Hospital. The results were as follows: 1) The gastric reflux was observed in 2.3% of 1,553 cases of routine Tc-99m DISIDA Hepatobiliary scintigraphy for 43 months. 2) Nineteen percent of patients with gastric reflux had the past medical history of operations on stomach or biliary system. And that history was more prevalent in patients with reflux than those without reflux, significantly (p<0.01). 3) On fiberoptic gastroduodenpscopic examination, 87% of the patients with gastric reflux had the gastroduodenal diseases such as gastritis, gastric ulcer, duodenal ulcer, gastric cancer, duodenal cancer and ampullary diverticulosis. We thought that the gastric reflux can be observed considerably in patients without any operation history on stomach or duodenum, although the operation history is more prevalent in patients with gastric reflux than those without reflux, significantly and most of patients with gastric reflux on routine Tc-99m DISIDA scan has various gastroduodenal diseases.

Full Text Available Technetiiim-99m is an ideal radionuclide with optimum decay characteristics. It can be obtained in sterile, pyrogen-free and carrier-free condition, as sodium pertechnetate (Na99mTcO4, from 99Mo/99Tc generator. Because of its six-hour physical half-life and monochromatic 140 keV photons free of -radiation, administration of small amounts of 99mTc solution is possible, without a significant radiation damage to the patient. Technetium eluted from the 99Mo/99mTc generator is in the highest oxidation form (+7. It can be used for diagnostic purposes alone, but it is often used for labeling different organic and inorganic compounds. As it is unreactive, reduction with a chemical reductant, (+1, (+3 and (+5 oxidation are necessary before use. Nowadays almost 80% of radiopharmaceuticals are based on 99mTc. Radiopharmaceuticals. Radiopharmaceuticals are radionuclides or radioactive compounds used in diagnosis and therapy of human diseases. A pharmaceutical is chosen based on its localization in the organ, or its participation in its physiological function. Radiation emitted from a radionuclide is detected by a radiation detector. The ability to incorporate available radionuclides into tracer molecules has been the main goal in developing radiopharmaceuticals. As radionuclides with nuclear characteristics used as either diagnostic or therapeutic radiopharmaceuticals, are predominantly metals, they can be designed as metal essential, whereby biological distribution is determined by coordination compound, or metal tagged, in which case the properties of the carrier molecule (ligand system determine the biological distribution. This paper reviews the development of 99mTc-radiopharmaceuticals. .

Identification of bacterial infection in orthopedic practice is an important issue for appropriate management. Conventional radiography including CT examination has limited role in such a situation. A Tc-99m Ciprofloxacin has been developed to localize bacterial infection in order to differentiate infection from inflammation. Critical evaluation of role of Tc-99m Ciprofloxacin scintigraphy in orthopedic practice was done in the present study. 104 patients with suspected infection in orthopedic clinic were taken up for Tc-99m Ciprofloxacin scintigraphy. A dose of 370 MBq of Tc-99m Ciprofloxacin was injected intravenously. Imaging was performed using Siemens integrated DIACAM camera with low energy all parallel or high-resolution collimators. Multiple spot views at serial time (1 hour, 4 hours and 24 hours) were obtained in 256 x 256 matrix size in ICON computer. Focal area of abnormal radionuclide concentration, which increased with time, was considered to be the pattern suggestive of presence of infection. In cases of equivocal qualitative appearance, quantitation of uptake was ascertained by the count statistics obtained using region of interest program. Final diagnosis of sepsis was based on microbiological examination or evidence of beneficial response to antibiotic therapy. Tc-99 Ciprofloxacin scintigraphy showed most favourable results in peripheral tubercular as well as non-tubercular osteomyelitis, tubercular arthritis and in cases with prosthesis (including vascular stent). It showed limited role in Pott's spine. The best sensitivity, specificity and accuracy of Tc-99m Ciprofloxacin using the defined criteria was 90%, 84% and 88% respectively in cases with non-tubercular osteomyelitis. Serial imaging up to 24 hours was required in ∼ 70% of cases. In ∼ 30% of cases quantification was required to form an opinion. We conclude that Tc-99m Ciprofloxacin is a highly useful technique in the management of infection in orthopedic practice. The procedure should

Scintigraphic image analysis of 99mTc-mertiatide (Mag-3, mercaptoacetyltriglycine) clearance provides the determination of the blood flow, the tubular transit time and the excretion as well from both kidneys. Radiopharmaceutical routine recommends a radiochemical purity control before administration of the product to a patient. The main objective of this study is to develop a Mag-3 labeling procedure that fits better than the previous one in our daily routine production of radiopharmaceuticals. Increasing proportions of 99mTc-Mag-3 were measured during the heating and cooling steps of the Mag-3 labeling procedure. High performance liquid chromatography (HPLC) analysis was used to confirm the results of a rapid radiochemical quality control assay on standard instant thin-layer chromatography-silica gel (ITLC-SG) paper. The reconstitution time takes 20-25 minutes from the harvest of pertechnetate to a ready-for-use calibrated patient syringe. The HPLC profile of 99mTc-Mag-3 including its minor impurities remains unchanged for 24-48 hours after reconstitution. The application of a programmable Peltier-directed device for heating/cooling provides a better control of the temperature course. The procedure proposed fully meets the labeling criteria recommended by the supplier and can be performed with a minimum of attention within a time-span that we formerly needed for solely the radiochemical purity control assay. Moreover, 99mTc-Mag-3 prepared in this way seems to be considerably more stable than mentioned in the manufacturer's instructions. (author)

The importance of clearance measurements in evaluating renal or hepatic function needs not further demonstration. The isotopic methods were proved in renal exploration but their utilization in exploration of hepato-biliary function needs to be evaluated. In this work we have compared the measurement of plasma clearance by Mebrofenine, a radiopharmaceutical of specifically hepatic elimination, with the reference method, the clearance of indocyanine green. On the basis of scintigraphic data from 23 patients who benefited by a hepato-biliary exploration by Mebrofenine-{sup 99m}Tc for pre-surgery account and surveillance, we have determined the plasma clearance of this radiopharmaceutical. The method makes use of the curve of normalized cardiac activity by a blood sampling, taken 60 minutes after injection. The measurement of the clearance of indocyanine green was effected within a delay inferior to 1 month from the moment of biliary scintigraphy. The average clearance of Mebrofenine-{sup 99m}Tc is of 553 ml/min for 1.73 m{sup 2} of corporal surface (typical interval is 374 ml/min), the value of indocyanine green is of 450 ml/min (typical interval is 229 ml/min). The two measurements of clearance are correlated (p = 0.05). In conclusion, the measurement of clearance by Mebrofenine-{sup 99m} appears to be adapted to the evaluation of hepato-biliary function

MDP kits for labelling with Tc99m were locally produced in different conditions, and the conditions for preparation were optimized. The quality control studies showed that the prepared kits were very good quality and comparable with that imported. Radiochemical purities ranged between 95-98% while reduced technetium ranged between 2-3% and free pertechnetate did not exceed 1%. Bioscan and biodistribution studies also showed high localization of Tc99m in the skeleton of rats and rabbits. (author). 8 refs., 14 tabs

A method of using /sup 99m/technetium for tagging excipients in medical diagnosis by scintigraphy comprises mixing, in an aqueous solution of alkali-metal pertechnetate, an excipient and a reducing agent in the form of a complex, which complex is such that the association constant of the anion with reduced techetium is less than the association constant of the excipient with reduced technetium, thereby forming a radio-pharmaceutical substance which is a complex between the excipient and /sup 99m/technetium.

Some physicochemical characteristics as well as pharmacokinetic behavior of 99mTc-PAH, as a novel renal agent, 99mTc-MAG3 and 131I-OIH were compared. 99mTc-PAH was prepared from lyophilized kit by adding 99mTcO4-. Labeled complex was stabile and high radiochemical purity radiopharmaceutical, with a low percentage of protein bound to human albumin and hydrophilic character. In spite of its smaller renal uptake, 99mTc-PAH gave satisfactory renal images, 99mTc-PAH showed faster urinary elimination than 99mTc-MAG3 and similar to those one for 131I-OIH. The comparison of pharmacokinetic parameters of 99mTc-PAH, 99mTc-MAG3 and 131I-OIH indicated the favorable characteristics of 99mTc-PAH. (author)

Full text: Bioavailability of drug administered topically in the liquid dosage form to the eye is limited due to rapid pre corneal clearance resulting from solution drainage and also spillage from palpebral fissure. With the objective of improving utilisation of drug by increasing its residence time in eye, topicamide, a mydriatic and cycloplegic agent was encapsulated into liposomes. Multi lamellar liposomes were prepared from soya phosphatidylcholine in combination with cholesterol, employing conventional lipid film hydration technique. Liposome dispersion was labelled with 99mTc-pertechnetate about 50 μCi in 15 μl of preparation was instilled in the eyes of the rabbit and dacryoscintigraphy was performed on a gamma camera fitted with a pinhole collimator. Dynamic and static images were taken. Three regions of interest namely conjunctival space, lacrimal sac and naso-lacrimal duct were marked and radioactivity in these regions over 10 minutes period was computed and compared with 99mTc-DTPA in aqueous phase. From these studies it was evident that there was increase in the residence time of liposome-bound radioactivity. Further, there was slower drainage of activity into lacrimal sac and nasolacrimal duct compared to 99mTc-DTPA. The half clearance times of activity in conjunctival space for Tc-DTPA, empty liposomes and drug-loaded liposomes were 3.22,15.21 and 16.8 min, respectively, while for lacrimal sac the values were 13.94, 29.09 and 29.2 min, respectively. This characteristic of the liposome-bound drug may be important in prolonging the therapeutic effect observed by us in rabbits

One of 99mTc-hexakis, 99mTc-methoxyisobutyl isonitrile (MIBI), has been demonstrated to have a myocardial uptake proportional to regional coronary blood flow. In this study, 99mTc-MIBI myocardial scintigraphy was performed for 16 patients with ischemic heart disease. After injection of 740 MBq of 99mTc-MIBI, 64 projection images were collected during a 360-degree rotation. Three-dimensional (3D) display of the left ventricle was reconstructed with depth-shading method from 99mTc-MIBI SPECT images, which were reconstructed by filtered back projection method. In 9 of the patients, left ventricular cineangiography were performed as diagnostic gold standard. Four physicians blinded to patients' clinical information interpreted 3D images and SPECT images on separate occasions. Diagnosis of hypoperfusion by 3D displays agreed with those of SPECT in 92.9% (104/112 segments), and disagreed in 7.1% (8 segments). Sensitivity and specificity of 3D images were 87.0% and 93.9%, which were not statistically different (p<0.05) from that of SPECT images (91.3%, 97.0%). Receiver operating characteristic (ROC) analysis revealed nearly identical curves for the two. Although 3D display had nearly identical diagnostic ability with SPECT, observers reported that 3D images were easier to diagnose than SPECT images. An advantage of the 3D display is that the display gives a more realistic impression of the left ventricle to an observer than tomography or planar imaging. Another advantage is that 3D display can reduce the amount of data storage compared with that of SPECT. In conclusion, 3D images may be useful for diagnosis of hypoperfusion of left ventricle. (author)

99mTc-Galactosyl human serum albumin (99mTc-GSA) is a new liver imaging radiopharmaceutical which specifically binds to the asialoglycoprotein-receptor on the liver cell membrane. We investigated the usefulness of 99mTc-GSA for evaluation of the liver function in patients with chronic liver damage. We calculated LHL15 for the index of hepatic uptake and HH15 for the index of clearance. In patients with liver cirrhosis, LHL15 value was higher and HH15 value was lower than those of other groups. Both decrease in LHL15 value and increase in HH15 value were correlated with the severity of the liver damage. Significant correlation ws also observed between the prolongation of ICG clearance and both decrease in LHL15 value and increase in HH15 value. In conclusion, these findings indicate that 99mTc-GAS can be a useful agent for evaluation of the liver function in patients with chronic liver damage. (author)

First clinical results have shown that among the 99mTc-complexes which were synthesized for renal function studies 99mTc-MAG3 revealed the most similar biokinetical characteristics compared with o-I-hippurate (OIH). Totally 90 simultaneous investigations of 12 kidney transplant patients were performed with 99mTc-MAG3 and 131I-OIH during the early post-transplantation period. It could be demonstrated that in case of an acute graft rejection or an acute tubular necrosis the respective renograms were qualitatively identical. Therefore, loss of information caused by using 99mTc-MAG3 instead of 131I-OIH could be excluded (BUBECK et al. 1987 b). During slope-clearance calculations after simultaneous application of both radiopharmaceuticals (n=16), volumes of distribution were revealed to be 11% for Tc-MAG3 and 16% for OIH related to the body weight. By determination of the plasma-protein binding, the glomerular filtered fraction of both substances were estimated to be 5 and 2% of the plasma activity for OIH and Tc-MAG3, respectively. Due to the negligible amount, which is eliminated by glomerular filtration, the clearance of Tc-MAG3 is a measure of its tubular extraction. It therefore may be termed as the 'Tubular Extraction Rate' (TER) of Tc-MAG3. From totally 103 simultaneous clearance-measurements with both 131I-OIH and 99mTc-MAG3 (88 were estimated on steady state conditions) the clearance-ration of Tc-MAG3/OIH was determined to be 0.67 (r=0.94). All these data yielded a 'Tubular Extraction Coefficient' (TEC) of 0.83 for OIH and 0.56 for Tc-MAG3. Derived from the known OIH-clearances in normal subjects an age-dependent formula for Tc-MAG3 was established: TER(MAG3) = 435.8-(3.03xage). Due to the hitherto known characteristics 99mTc-MAG3 can clinically be used as a substitute for radioiodinated OIH in both application areas, renal imaging and quantitative function studies of the kidneys. (orig.)

Radioisotope Tc-99m is widely used for variety of nuclear medicine diagnostic procedures. For many commercial applications, it is prepared in a portable type generator. Nuclear Malaysia has been producing a dry type alumina chromatographic column generator utilizing fission Mo-99. This injectable Tc-99m must meet the British Pharmacopeia [1] product specification prior to be apply on patient. This paper provides a method to minimize the up to acceptable level Mo-99 in the final product. Purposely made pertechnetate contaminated with Mo-99 and re-eluate by using old generator. Excellent removal of Mo-99 impurity was achieved and more than 80 % of Tc-99m total activity was recovered. (author)

The preparation, application and clinical usage of 99mTc-mercaptoacetyltriglycine, MAG3, a tubular secreted compound, is described in the first 225 patients in a phase III study. Image quality, relative renal function, and renal transit times were compared with a 4 fold greater administered activity of 99mTc-DTPA in 11 patients. Correlation coefficients of 0.94 for relative function, 0.83 for parenchymal transit time index and 0.82 for whole kidney transit time index were found. Frusemide responses were similar. 99mTc-MAG3 is an efficacious radiopharmaceutical for routine renal radionuclide studies, giving excellent image quality in patients with hypertension, poor renal function, obstructive nephropathy or a renal transplant. (orig.)

Four 99mTc-MAG3-biotin conjugates were synthesized to determine their potential use in antibody pretargeting strategies for radioimmunoscintigraphy (RIS). To use these 99mTc-MAG3-biotin conjugates as model compounds for 186Re-MAG3-biotin conjugates for radioimmunotherapy (RIT), nanomolar amounts of 99Tc were added as carrier to 99mTc. The biotin derivatives used for the preparation of the conjugates - biocytin, biotin hydrazide, biotinyl-piperazine, and biotinyl-diaminosuccinic acid - differed at the site that is regarded to be susceptible to hydrolysis by biotinidase present in human plasma. All four conjugates were produced with high radiochemical purity, were stable in PBS, and demonstrated full binding capacity to streptavidin. The 99mTc/99Tc-MAG3-labeled biotinyl-piperazine and biotinyl-diaminosuccinic acid conjugates were stable in mouse as well as human plasma, whereas the corresponding biocytin and biotin hydrazide conjugates were rapidly degraded. The biodistribution in nude mice at 30 min after injection was similar for all conjugates, and a rapid blood clearance and high intestinal excretion were both observed. It is concluded that the metabolic routing of a conjugate containing biotin and MAG3 is dominated by these two moieties. For this reason, MAG3-biotin conjugates do not seem suited for pretargeted RIT, for which quantitative and fast renal excretion is a prerequisite to minimize radiation toxicity. However, in a pretargeted RIS approach the 99mTc-MAG3-biotin conjugates might have potential

The aim of this study was to establish a simple and accurate procedure to calculate the unilateral effective renal plasma flow (ERPF) using 99mTc-MAG3 gamma-camera renography. Eleven patients with urological disorders were studied with 99mTc-MAG3 to calculate the renal uptake ratio (RUR), which was defined as the ratio of absorption-corrected renal counts within 1-2 min after intravenous injection to injection radioactivity measured with a gamma-camera. We assumed that 99mTc-MAG3 was distributed in the circulation, moved from the circulation to the kidneys, and was excreted solely from the kidneys. We thus adopted an one-compartment model to calculate 99mTc-MAG3 clearance (CLMAG) using RUR. Sequential p-aminohippurate (PAH) clearance study was performed as a gold standard in all the patients to compare CLMAG and PAH clearance. Obtained CLMAG correlated well with PAH clearance, and this one-compartment model seemed appropriate for describing CLMAG. Unilateral ERPF was accurately measured within two minutes after the intravenous injection of 99mTc-MAG3 in conjunction with the renal imaging study. This procedure is simple and reliable, and requires no blood or urine sampling. (author)

The sorption of 99mTcO4- from polluted waters to the surficial organic-rich sediments was measured, in laboratory and field conditions. Batch experiments were used in the laboratory tests to study the influence of Tc-concentration, redox potential and liquid to solid ratio. While in aerated water no Tc sorption was observed, in water with heavy loads of domestic sewage, under strong anaerobic conditions, slight sorption was detected, indicating that Tc can be reduced in these conditions. The reduction rate shows no dependence on Tc-concentration in the range from 5 x 10-16 M to 5 x 10-9 M, but some influence of the liquid to solid ratio can be observed. The results from laboratory experiments have been confirmed in a field double tracing experiment, performed at two locations of the Almendares river basin. 99mTcO4- and Rhodamine WT-20% were injected simultaneously and the RTD-curves registered downstream. The recovery calculations and the shapes of the curves in each site showed no retardation or sink of technetium in the experimental conditions. This result is consistent with the laboratory behavior previously observed and supports the hypothesis that Tc sorption is mainly a function of the redox potential of the system. The suitability of 99mTcO4- short term hydrological studies in streams polluted with domestic sewage, is concluded. (author)

As recently shown, angiogenesis is the most reliable marker of breast cancer invasiveness. Unfortunately it must be assessed by immunohistochemistry on tissue specimens. We have used technetium-99m sestamibi, a marker of regional blood flow in other organs that often but not always images breast cancer, to assess the invasiveness of this tumour. Nineteen patients, ten with nodal metastases and nine without any metastases, were studied with 99mTc-sestamibi scintigraphy before operation. Angiogenesis was quantitatively assessed by immunohistochemical staining of endothelia for factor VIII. All the node-positive (N+) patients at surgical revesion showed a positive 99mTc-sestamibi scan of the primary tumour and all the N-patients were negative. Nine out of ten N+ and sestamibi-positive tumours showed more than 135 microvessels/mm2 and one showed 99 microvessels/mm2; by contrast there were 71.6±12.1 microvessels/mm2 in the nine N- and sestamibi-negative tumours. Our study suggests that 99mTc-sestamibi is a marker of breast cancer invasiveness: its uptake is related to angiogenesis and, possibly, to oxidative metabolism of the tumour. (orig.)

As recently shown, angiogenesis is the most reliable marker of breast cancer invasiveness. Unfortunately it must be assessed by immunohistochemistry on tissue specimens. We have used technetium-99m sestamibi, a marker of regional blood flow in other organs that often but not always images breast cancer, to assess the invasiveness of this tumour. Nineteen patients, ten with nodal metastases and nine without any metastases, were studied with [sup 99m]Tc-sestamibi scintigraphy before operation. Angiogenesis was quantitatively assessed by immunohistochemical staining of endothelia for factor VIII. All the node-positive (N+) patients at surgical revesion showed a positive [sup 99m]Tc-sestamibi scan of the primary tumour and all the N-patients were negative. Nine out of ten N+ and sestamibi-positive tumours showed more than 135 microvessels/mm[sup 2] and one showed 99 microvessels/mm[sup 2]; by contrast there were 71.6[+-]12.1 microvessels/mm[sup 2] in the nine N- and sestamibi-negative tumours. Our study suggests that [sup 99m]Tc-sestamibi is a marker of breast cancer invasiveness: its uptake is related to angiogenesis and, possibly, to oxidative metabolism of the tumour. (orig.)

Osteomyelitis, which is characterized by progressive inflammatory destruction and new opposition of bone, is still a difficult infection to treat. The clinical diagnosis in late stages is achieved easily, but an early diagnosis is more challenging. Staphylococcus aureus is a common agent found in osteomyelitis and bone prostheses infection. Diagnosis by scintigraphy has advantages because it is a non-invasive procedure and is able to perform an early diagnosis even before anatomic changes. Thus, nuclear medicine could contribute to an accurate diagnosis since specific radiopharmaceuticals were developed. In this study, aptamers selected to Staphylococcus aureus were labeled with {sup 99m}Tc and used for bacteria identification in an osteomyelitis experimental model. The aptamers selected to S. aureus were directly labelled with {sup 99m}Tc and were evaluated by biodistribution studies. Wistar rats with intraosseous infection in the right paw were used. A random aptamer labelled with {sup 99m}Tc was as control. Six animals were used in each group. The aptamers labeled with {sup 99m}Tc were able to identify the infection foci caused by S. aureus displaying a target/non-target ratio of 2,23 ± 0,20, after 3 h. The control group presented a target/non-target ratio 1,08 ± 0.23. The results indicated that the radiolabeled aptamers were able to identify specifically the infection foci and they should be further explored for infection diagnosis by scintigraphy. (author)

A case of 99m Tc-MDP deposition in the testes of a patient who was submmited to therapeutic orquiectomy for prostatic adenocarcinoma six years ago, during bone scintigraphy, is reported. A brief review of the pertinent literature has been made with discussion of the possible mechanism justifying the finding. (Author)

203Hg-chlormerodrin has been widely used for renal scintigraphy in Japan, but it is not the best scintigraphic agent because of the large exposure dose to the kidneys. Renal scintigraphy with sup(99m)Tc-DMS (dimercaptosuccinate) was performed on 36 patients suspected of having various renal disorders. The scintigraphic images with sup(99m)Tc-DMS were similar to those with 203Hg-chlormerodrin. Urinary excretion and kidney accumulation of sup(99m)Tc-DMS were measured, and the renal images were obtained at various times ranging from 5 min to 24 hr after injection in 6 normal subjects. Approximately 30% of the administered radioactivity was excreted in the urine within 24 hr of injection. Kidney-to-background ratios rose sequentially with time, and renal image quality was better on scintiphotos obtained 2 hr or more after injection. No side effects were observed in this study. In conclusion, sup(99m)Tc-DMS was proved to be useful for renal static imaging and also for vascular dynamic studies. (auth.)

A phase I clinical study on 99mTc-hexakis 2-methoxy isobutylisonitrile (99mTc-MIBI) was carried out in 6 normal volunteers. There was no significant change in vital signs and laboratory parameters attributing to the reagent other than complaint of slight and transient metallic taste immediately after the injection in 4 volunteers. The highest dosimetry was calculated as 1.1 mGy/37 MBq at lower large intestine, which was within the acceptable range. 99mTc-MIBI was rapidly cleared from the blood and accumulated in the heart immediately after the injection with 1.4% dose and 1.8% dose at 5 min at rest and at stress, respectively. The retention of radioactivity in the heart well continued for at least several hours. The heart-to-lung ratio was over 2.00 at 5 min and heart-to-liver ratio was over 1.00 at 60 min. Myocardial planar and SPECT images were obtained with high quality. In conclusion, 99mTc-MIBI is a useful myocardial perfusion imaging agent. (author)

A method of preparing methylene diphosphonic acid disodium salt is described together with a method of preparation and quality control of its lyophilization form containing stannous chloride, which serves for the preparation of the 99m-technetium medronate injection. The injection is used as a diagnostic means for bone skeleton imaging. (author) 2 figs., 7 refs

A method of fibrinogen preparation is presented in order to label it with 99mTc employing Sn as reducing agent in alkaline medium. Purity controls by chromatography, coagulation in rabbits and biodistribution in rats were performed. It is concluded that optimal time incubation is between 22 and 23 hs. (M.E.L.)

The ideal radioisotope for single photon emission computed tomography imaging is 99mTc, due to its physical decay characteristics, its availability through commercially available generator systems and its low cost per dose. Technetium-99m hydrophilic complexes are used to evaluate the integrity of the blood-brain barrier, while neutral and lipophilic complexes are used as brain perfusion imaging agents for determination of changes in regional cerebral blood flow in various neurological disorders. Radiopharmaceuticals that bind to central nervous system (CNS) receptors in vivo are useful for understanding the pathophysiology of a number of neurological and psychiatric disorders, their diagnosis and treatment. Nowadays, CNS receptor imaging agents are, with some exceptions, typically positron emission tomography radionuclide based radiopharmaceuticals. The reason for this is not based on principal but is rather as a result of the fact that efforts in the direction of 99mTc containing agents have not been strong or consistent enough. In the chapter, the progress made in the development of 99mTc complexes for imaging dopamine transporter, 5-HT1A receptor and amyloid plaques is presented. (author)

In nuclear medicine studies, 99mTc-Dimercaptosuccinic acid (99mTc-DMSA) has been shown to be an excellent radiopharmaceutical agent for detecting focal abnormalities of the renal cortex in patients. The agent, however, oxidizes readily and must be used within 30 minutes of preparation. The instability of the radiopharmaceutical renders the kit less economical to use. Several factors affecting the labeling yield such as the kit formulation, stannous and stabilizer content were investigated. The radiochemical determination of the radiolabelled product was analyzed using I TLC-SG system developed in methyl ethyl ketone and the radiolabelled 99mTc-DMSA biological distributions were carried out in female rats. Stability study of the radiolabelled 99mTc-DMSA was carried out using ascorbic acid as stabilizer. Comparative study was also carried out on both the prepared kit and those obtained commercially. The DMSA kit was successfully developed and the result obtained was found to be comparable to that of the commercially available kit. (Author)

Osteomyelitis, which is characterized by progressive inflammatory destruction and new opposition of bone, is still a difficult infection to treat. The clinical diagnosis in late stages is achieved easily, but an early diagnosis is more challenging. Staphylococcus aureus is a common agent found in osteomyelitis and bone prostheses infection. Diagnosis by scintigraphy has advantages because it is a non-invasive procedure and is able to perform an early diagnosis even before anatomic changes. Thus, nuclear medicine could contribute to an accurate diagnosis since specific radiopharmaceuticals were developed. In this study, aptamers selected to Staphylococcus aureus were labeled with 99mTc and used for bacteria identification in an osteomyelitis experimental model. The aptamers selected to S. aureus were directly labelled with 99mTc and were evaluated by biodistribution studies. Wistar rats with intraosseous infection in the right paw were used. A random aptamer labelled with 99mTc was as control. Six animals were used in each group. The aptamers labeled with 99mTc were able to identify the infection foci caused by S. aureus displaying a target/non-target ratio of 2,23 ± 0,20, after 3 h. The control group presented a target/non-target ratio 1,08 ± 0.23. The results indicated that the radiolabeled aptamers were able to identify specifically the infection foci and they should be further explored for infection diagnosis by scintigraphy. (author)

99mTc dimercaptosuccinic acid (DMSA) is filtered through the glomeruli and reabsorbed by the proximal tubules as low molecular weight proteins. In Lowe syndrome this mechanism is impaired and so poor DMSA uptake is seen. Poor DMSA uptake was shown in very few studies, but none mentioned normal 99mTc MAG3 uptake. In this case, the patient had poor DMSA uptake, normal MAG3 uptake and a neurogenic bladder in anterior to the left kidney that attenuates left kidney. (author)

Tc-99m dimercaptosuccinic acid (DMSA) is filtered through the glomeruli and reabsorbed by the proximal tubules as low molecular weight proteins. In Lowe syndrome this mechanism is impaired and so poor DMSA uptake is seen. Poor DMSA uptake was shown in very few studies, but none mentioned normal Tc-99m MAG3 uptake. In this case, the patient had poor DMSA uptake, normal MAG3 uptake and a neurogenic bladder in anterior to the left kidney that attenuates left kidney. PMID:23559713

A 43-year-old woman with diabetic nephropathy underwent a Tc-99m MAG3 renal scintigraphy for the evaluation of renal function. Posterior images at 60 minutes demonstrated a migration of radiotracer activity beyond the lower pole of the left kidney, which might be incorrectly interpreted as urine leaks. However, the increased activities were moving along the bowel lumens over time. Another ring-like radioactivity was also seen in the suprasplenic region, and increased with time. These radioactivities were in the gastric fundus and gastrointestinal tract and caused by free Tc-99m pertechnetate

Scintigraphic imagery was used in breast carcinoma mostly for the bone metastases screening, using 99mTc-MDP. Others radiopharmaceuticals can be used to visualize either the primary tumour or the soft tissues metastases. It's mainly the case of 99mTc-MIBI, and also of some somatostatin analogues, like Octreoscan. This case report of a patient with a T3N1M+ breast adenocarcinoma having different secondary sites represent also a prove of the complementarity of these explorations, which give the possibility of diagnostic and therapeutic evaluation and, in the same time, the possibility of a better understood of the metastasizing mechanism. PMID:9455458

Perfusion lymphoscintigraphy was performed by subcutaneous injection of 7.4 MBq (0.2mCi) {sup 99m}Tc-human serum albumin ({sup 99m}Tc-HSA) on 18 patients with uterine cancer treated by operation and/or irradiation. Radioactivity at the injection site was counted for 3 min at 10 min (a) and at 3 hr (b) after injection, and the clearance of {sup 99m}Tc-HSA was defined as (1-(b)/(a)) x 100(%) ((a) and (b) were corrected for decay of the isotope). The clearance in 6 legs with lymphedema was significantly more delayed than that in 16 legs without lymphedema in the patients treated with both surgery and irradiation (16.6 +- 7.7% vs 34.9 +- 9.3%: P< 0.01). The clearances in edematous legs in a case which had developed a venous occulusion after operation were 44.2% and 41.7%, which were almost the same as those in the non-edematous patients treated with surgery alone. The clearance in patients treated with both operation and irradiation was significantly more delayed than that in patients treated with the signle modality of operation or irradiation (29.7 +- 11.9% vs 41.1 +- 7.2%, 44.5 +- 7.7%, respectively: P< 0.01). These data suggest that perfusion lymphoscintigraphy using {sup 99m}Tc-HSA is useful for evaluating patients with lymphedema and for differentiating it from edema caused by other mechanisms. (author).

The aim of the present work was to study the biological and radiochemical behaviour of two somatostatin analogues, the RC-160 and Tyr3Octreotide(TOC) peptides when labelling with 99mTc by two methods: direct and indirect using S-benzoyl- mercaptoacetyl triglycine (MAG-3) and hydrazinonicotinamide (HYNIC) as chelating agents. RC-160 was labelled with 125I (30% labelling yield) in order to examine its receptor specificity and to study the biodistribution in normal animals. A total binding of 30% and a non specific binding lower than 10% was obtained. On the other hand, the RC-160 was labelled with 99mTc by a direct method (70% labelling yield), using sodium ascorbate and dithionite in order to reduce the peptide and 99mTc, respectively. The synthesis of RC-160 with S-benzoyl MAG-3 and TOC with HYNIC, for labelling with 99mTc are also described. The conjugates were prepared on a small scale and labelled with the radionuclide using tricine as co-ligands for HYNIC conjugates. Chromatographic studies were performed using HPLC system and radiochemical purities higher than 75% and 95% were obtained respectively. Biodistributions studies in normal Wistar rats were performed and results were correlated with chromatographic and protein binding properties. Lower lipophilicity of the labelled conjugates resulted in a higher renal excretion. HYNIC-TOC complex showed promising results when labelling with 99mTc using tricine as co-ligand although higher stability should be found for ternary co-ligands compared to tricine. (author)

Technetium-99m (6.02 h) is the most widely used radioisotope in nuclear medicine, accounting for more than 80% of all diagnostic nuclear medicine procedures. It is almost exclusively produced from the decay of its parent 99Mo. The present sources of 99Mo are research reactors by using the (n,γ) nuclear reaction with natural Mo (98Mo, ∼24%), resulting in inexpensive but low-specific activity 99Mo, or by neutron-induced fission of 235U, which results in expensive but high specific activity 99Mo. This publication covers several aspects related to the production of 99Mo and 99mTc. The contributed papers reflect the current status of the technology and discuss potential alternative methodologies for the production of 99Mo and 99mTc for medical use. The first four papers address the technologies using nuclear reactors, including the description of a new method using an aqueous homogenous reactor core for production of fission 99Mo and the latest development efforts to fabricate 235U low enriched targets (LEU, 235U). The next five papers discuss the potential of utilizing particle accelerators and assess the current status of the available nuclear data for the production of both, 99Mo and 99mTc with proton and deuteron beams. The last paper discusses a new technology based on gel system for the preparation of 99Mo/99mTc generators using low specific activity 99Mo produced in research reactors by the neutron activation of natural and inexpensive molybdenum oxide targets. Each individual paper was indexed and abstracted

Even with rapid technological development in the field of diagnostic imaging, the localization of infection continues to pose challenges in day-to-day routine clinical practice. Tc-99m Ciprofloxacin is a relatively new radiopharmaceutical, which has proven its utility in imaging infection. This paper presents a new method of labeling Ciprofloxacin with Tc-99m using SnCI2.2H20 as reducing agent. The procedure used 2 mg of Ciprofloxacin manufactured by Bayer, 400 μg of SnCI2.2H20 (Sigma Chemical Co.) and 185MBq of Technetium-99m in the form of pertechnetate (Tc-99mO4) in a volume of 300 μl. The labeling was carried out at 100 deg. C for 10 minutes and at ambient temperature for a similar period of time. The solution obtained was filtered using millipore filter of 0.22 μm size. The efficiency of the labeling, verified by ascending chromatography on Whatman No.1 paper was found to be 97.3 % (±1.6), while it was 96.8% (±2.3) using Whatman No.3 paper and 96.6% (± 2.1) using thin-layer chromatography. Chromatography by exclusion chromatography (Bio-Gel P 10) was used for confirmation of the above results. The labeled molecules were eluted first, followed by the molecules of Technetium-99m while the colloids remained attached to the column. The results of the present study are comparable with the results of previous studies reported in literature. (author)

To evaluate the clinical significance of RI images of hepatic blood flow using Tc-99m-PMT, analysis of the RI images and estimation of hepatic blood flow were carried out in patients with various liver diseases (37 cases). After intravenous injection of Tc-99m-PMT, hepatic accumulation curve of ROI positioned at whole liver area and time activity curve of ROI positioned at celiac artery were obtained through scintillation camera images with the computer-analysed system. Hepatic blood flow coefficient (K) was calculated from the hepatic accumulation curve. Based on the differential curve calculated from the time activity curve, chronological images of arterial, portal, parenchymal and saturated parenchymal phases were obtained. Results ; 1) K was 0.50 + 0.04, 0.35 + 0.02 and 0.26 + 0.04/min in normal type, CH type and LC type respectively. These coefficients well correlated with clinical severity of hepatic diseases. 2) Perfusional phase images of the liver became poorer in accordance with progression of liver disease, while images of spleen, portal venous system and collateral channels were more clearly obtained in liver cirrhosis. This method was shown to have a potential to understanding of severity of liver disease and hepatic blood flow dynamics.

To evaluate the clinical significance of RI images of hepatic blood flow using Tc-99m-PMT, analysis of the RI images and estimation of hepatic blood flow were carried out in patients with various liver diseases (37 cases). After intravenous injection of Tc-99m-PMT, hepatic accumulation curve of ROI positioned at whole liver area and time activity curve of ROI positioned at celiac artery were obtained through scintillation camera images with the computer-analysed system. Hepatic blood flow coefficient (K) was calculated from the hepatic accumulation curve. Based on the differential curve calculated from the time activity curve, chronological images of arterial, portal, parenchymal and saturated parenchymal phases were obtained. Results ; 1) K was 0.50 + 0.04, 0.35 + 0.02 and 0.26 + 0.04/min in normal type, CH type and LC type respectively. These coefficients well correlated with clinical severity of hepatic diseases. 2) Perfusional phase images of the liver became poorer in accordance with progression of liver disease, while images of spleen, portal venous system and collateral channels were more clearly obtained in liver cirrhosis. This method was shown to have a potential to understanding of severity of liver disease and hepatic blood flow dynamics. (author)

Prostate-specific membrane antigen (PSMA) is expressed strongly in prostate cancers and is, therefore, an attractive diagnostic and radioimmunotherapeutic target. In contrast to previous reports of PMSA-targeting (99m)Tc-tricarbonyl complexes that are cationic or lack a charge, no anionic (99m)Tc-tricarbonyl complexes have been reported. Notably, the hydrophilicity conferred by both cationic and anionic charges leads to rapid hepatobiliary clearance, whereas an anionic charge might better enhance renal clearance relative to a cationic charge. Therefore, an improvement in rapid clearance would be expected with either cationic or anionic charges, particularly anionic charges. In this study, we designed and synthesized a novel anionic (99m)Tc-tricarbonyl complex ([(99m)Tc]TMCE) and evaluated its use as a single-photon emission computed tomography (SPECT) imaging probe for PSMA detection. Direct synthesis of [(99m)Tc]TMCE from dimethyl iminodiacetate, which contains both the asymmetric urea and succinimidyl moiety important for PSMA binding, was performed using our microwave-assisted one-pot procedure. The chelate formation was successfully achieved even though the precursor included a complicated bioactive moiety. The radiochemical yield of [(99m)Tc]TMCE was 12-17%, with a radiochemical purity greater than 98% after HPLC purification. [(99m)Tc]TMCE showed high affinity in vitro, with high accumulation in LNCaP tumors and low hepatic retention in biodistribution and SPECT/CT studies. These findings warrant further evaluation of [(99m)Tc]TMCE as an imaging agent and support the benefit of this strategy for the design of other PSMA imaging probes. PMID:27073053

Pulmonary clearance of small droplet 99mTc-DTPA radioaerosol was studied in 100 patients (12 normal subjects, N; 10 asymptomatic healthy smoker, FA; 31 patients with interstitial lung diseases, IP; 47 patients with chronic obstructive lung disease, BPCO). The first seven minutes of clearance were described with the function At=Ao*exp(-K*t) and the time constant K was considered representative of the 99mTc-DTPA clearance rate and hence of the alveolar-capillary barrier permeability. Groups FA, IP and BPCO showed a significant (p99mTc-DTPA dynamic lung scanning is an easy, non-invasive method to assess derangements of alveolar-capillary barrier permeability secondary to epithelial damage; 2) permeability increase is a very early effect of cigarette smoke damafe to the epithelium; 3) other mechanisms of epithelial injury are present in diffuse lung disease; 4) while the clinical role of this new pathophysiological test is not yet clear, it is likely that it may become a very early marker of pulmonary epithelial damage in diffuse lung disease

Introduction: To enable imaging at an earlier time after injection, a radiopharmaceutical with higher affinity for bone, larger ratio of bone-to-soft tissue uptake and more rapid clearance from blood is required. The nature of diphosphonic acid is a key factor to determine the advantages of the radiopharmaceuticals. The purpose of this study is to optimize the linker chain between the imidazolyl and geminal diphosphonate group in the zoledronic acid (ZL) to develop novel single photon emission computed tomography (SPECT) bone imaging agent. Methods: A novel ZL derivative, 1-hydroxy-3-(1H-imidazol-1-yl)propane-1,1-diyldiphosphonic acid (IPrDP), was successfully prepared and labeled with {sup 99m}Tc in a high labeling yield. Biodistribution of {sup 99m}Tc-IPrDP and {sup 99m}Tc-ZL in normal mice were studied and compared. SPECT bone scanning was performed on the rabbit and a series of dynamic and static images were recorded by Philips SKY Light emission computed tomography. Results: In the biodistribution studies, {sup 99m}Tc-IPrDP exhibits significant advantages on the bone resorption and the clearance from soft tissues compared with {sup 99m}Tc-ZL. Kinetics of blood clearance in mice showed that T{sub 1/2{alpha}} and T{sub 1/2{beta}} of {sup 99m}Tc-IPrDP were 1.47 min and 46.47 min, while those of {sup 99m}Tc-ZL were 2.28 and 52.63 min respectively. Excellent images of the rabbit skeleton can be quickly obtained for {sup 99m}Tc-IPrDP, which was faster than {sup 99m}Tc-ZL and the clinically widely used bone imaging agent {sup 99m}Tc-MDP (technetium-99m labeled with methylenediphosphonate). Conclusions: {sup 99m}Tc-IPrDP possesses excellent characteristics for the potential application as a novel bone scanning agent.

Objective. We present preliminary results of a new method (hereinafter called 'CT-clearance') to measure single kidney contrast media clearance by performing multiphasic helical CT of the kidneys. CT-clearance was calculated according to an extension of the Patlak-Plot. In contrast to prior investigators, who repeatedly measured a single slice, this method makes it possible to calculate single kidney clearance from at least three spiral CTs, utilizing the whole kidney volume. Methods. Spiral CT of the kidneys was performed unenhanced and about 30 and 100 s after administration of about 120 ml iopromide. Sum-density of the whole kidneys and aortic density was calculated from this data. Using this data, renal clearance of contrast media was calculated by CT-clearance in 29 patients. As reference, Serum-clearance was calculated in 24 patients by application of a modified one-exponential slope model. Information on the relative kidney function was gained by renal scintigraphy with Tc99m-MAG-3 or Tc99m-DMSA in 29 patients. Results. Linear regression analysis revealed a correlation coefficient of CT-clearance with Serum-clearance of r=0.78 with Cl (CT) [ml/min]=22.2+1.03 * Cl (serum), n=24. Linear regression of the relative kidney function (rkf) of the right kidney calculated by CT-clearance compared to scintigraphy results provided a correlation coefficient r=0.89 with rkf(CT)[%]=18.6+0.58 * rkf(scintigraphy), n=29. Conclusion. The obtained results of contrast media clearance measured by CT-clearance are in the physiological range of the parameter. Future studies should be performed to improve the methodology with the aim of higher accuracy. More specifically, better determination of the aortic density curve might improve the accuracy

A new lymph node radio-imaging agent, technetium-99m polyphase liposome oleatis (99mTc-plo), has recently been developed. Polyphase liposome oleatis was labelled with radionuclide by stannous chloride method. The labelled rate was 90% or more as technically identified by thin layer chromatography, external gamma-camera imaging and radioautography. In animal experiment, 0.2-0.3 ml (0.2 mci) of the 99mTc-plo was injected subcutaneously into the toes web of rats. After half an hour, the regional lymph nodes of popliteal fossa were visualized very clearly. The imaging figures may keep their distinct shadow up to 24 hours. The tested rabbits were sacrificed 10 hours after 99mTc-plo injection for detecting various kinds of tissue and organ with a scintillation counter. The regional lymph nodes revealed the highest uptake rate of the new agent, 12,116; 1,303; 1,615 times higher than that of the adjacent muscles, liver and spleen, respectively. In clinical experiment, 0.2-0.3 ml (0.5-0.8 mci) of the 99mTc-plo was injected subcutaneously into the toes web of patients. Half an hour later, the lymph nodes of inguinal, external iliac and common iliac regions appeared in sequence. If the new agent is injected perianally, the internal iliac lymph nodes will be seen. No side effect was observed in both types of experiment. This new agent has been tried in rats, rabbits and dogs with similar positive results. The new lymph node imaging technique is simple, safe, reliable and reproducible. This agent, being directed toward the lymph nodes and possessing affinity to cancer cells, is expected to be supplementary method to CT and B-ultrasonography for detecting lymphoid malignancy and lymph node metastasis. PMID:3248482

Background: The technetium 99m ({sup 99m}Tc)-radiolabeled, leukocyte-avid peptide-glycoseaminoglycan complex, [{sup 99m}Tc]P1827DS, has been synthesized as an improved infection/inflammation imaging agent to [{sup 99m}Tc]P483H (LeukoTect, Diatide). In a phase I/II clinical trail, [{sup 99m}Tc]P483H images were equivalent to those obtained with {sup 111}In ex vivo labeled leukocytes. However, there was physiologic accumulation of radioactivity in the body that could hamper interpretation of the images. In this study, the potential of [{sup 99m}Tc]P1827DS for infection imaging was assessed in comparison with [{sup 99m}Tc]P483H and the well-described imaging agent [{sup 99m}Tc] hydrazinonicotinamide (HYNIC)-interleukin 8 (IL-8). Methods: The binding of [{sup 99m}Tc]P1827DS to human blood cell was studied in vitro. A rabbit Escherichia coli infection model was used to perform the biodistribution and imaging studies with [{sup 99m}Tc]P1827DS, [{sup 99m}Tc]P483H and [{sup 99m}Tc]HYNIC-IL-8. Results: [{sup 99m}Tc]P1827DS binds to leukocytes but not to erythrocytes. The leukocyte binding was not saturable up to an investigated concentration of 10 {mu}M. The accumulation of [{sup 99m}Tc]P1827/DS at the infection site strongly depends on the P1827/DS ratio and was optimal at a molar ratio of 10:1. [{sup 99m}Tc]P1827DS shows improved biodistribution over [{sup 99m}Tc]P483H with similar uptake at the infection site. Abscess uptake of [{sup 99m}Tc]HYNIC-IL-8 was approximately three times higher than that of [{sup 99m}Tc]P1827DS. [{sup 99m}Tc]HYNIC-IL-8 showed high accumulation in the kidneys, whereas [{sup 99m}Tc]P1827DS showed high lung uptake and slightly higher accumulation in the liver and spleen. Conclusion: [{sup 99m}Tc]P1827DS is a potential new inflammation imaging agent, which clearly visualized the abscess in the rabbit E. coli infection model and showed improved biodistribution compared to [{sup 99m}Tc]P483H. However, the infection uptake and biodistribution of

Full text: The aim of this study was to assess the role of the Tc-99m Tetrofosmin (TF) in conjunction with Tc-99m methylenediphosphonate (MDP) in pre-surgical breast cancer (BC) staging. Thirty-six female patients, age range was 32-70 years (average 51.45 years), where the clinical examination, mammography (MG) and fine-needle aspiration cytology were inconclusive were subjected to Tc-99m TF Scintimammography (SMM). All the patients were examined in a specialized breast clinic by experienced surgeons and radiologists. Of the 36 patients, 24 had hyperdense breasts, 8 had undergone lumpectomy or mastectomy due to cancer in one of the breasts and were included in the present study because of suspicion of lesion in the contra lateral breast, 2 had palpable axillary lymph nodes (LN) but no palpable breast lump and 2 patients were of mastitis carcinomatosis. All biopsies were histopathologically verified 740 MBq of Tc-99m TF (Myoview-Amersham) was injected in the arm opposite to the side of the breast lesion. In patients with bilateral breast lesions (BL) radiopharmaceutical was injected in a pedal vein. Planar imaging in prone position was done 10-15 min later. Two lateral views of the left and right breasts including axilla were acquired followed by an anterior view in supine position with arm in an upright position so as to include both breasts and axillary region in the field of imaging view. Imaging was done using a large field of view single-head gamma camera (Diacam-Siemens) coupled with low-energy high-resolution collimator. In patients with locally advanced BC who were to receive pre-operative neo-adjuvant chemotherapy, cardiac GATED SPECT was also acquired using standard protocol. After few days, Tc-99m MDM scintimammography and whole-body bone scintigraphy was also performed. SMM, using the same acquisition protocol as with 99mTc-TF, was done 5-10 min after intravenous injection of 555-740 MBq 99mTc MDP. Standard WBBS was acquired two to three hours later. SMM

Technetium-99m-diethylenetriaminepentaacetic acid-galactosyl-human serum albumin (99mTc-GSA) is a new liver scintigraphy agent which binds to asialoglycoprotein receptor in hepatocyte. Studies were performed in three normal volunteers and 11 patients with liver cirrhosis. Time-activity curves for the heart and liver were obtained for 60 min following an i.v. injection of 99mTc-GSA (1 mg/185 MBq). We introduced five compartments to describe 99mTc-GSA: 1) extrahepatic blood, 2) hepatic blood, 3) receptor, 4) interstitial fluid and 5) urine. The %ID of 99mTc-GSA in blood and the hepatic blood volume were obtained from the extrapolation of the biexponential fitting for the heart and liver curves. Michaelis-Menten type saturation kinetics was applied to the process of receptor-ligand binding. Numerical analysis solved the simultaneous differential equations that were introduced from the compartment model. Hepatic blood flow was 1,651±131 ml/min, maxial removal rate for the ligand was 0.547±0.069 mg/min in normal controls. Both results were significantly decreased in patients with liver cirrhosis compared with normal controls. Present study may provide a novel method for the diagnosis of liver function that allows independent quantification of the hepatic blood flow and the receptor population. (author)

The aim of this study was the evaluation of a new method, dynamic renal scintigraphy in zoom mode using Tc-99m-DTPA with deconvolution of renographic curves in evaluation of morphology and function of the kidney and upper urinary tract in children with various degrees of vesicoureteral reflux. For the first time we used our own method generating 6 functional images of the mean time in deconvolution of renographic curves which offers better detectability of pathologic changes in the kidney using dynamic scintigraphy. In the analysis of functional images of the mean time retention of activity was noticed within anatomic structures of a kidney, parenchyma, calyces as well as the renal pelvis. Time activity curves generated over focal retention in the parenchyma, found in the late functional images of the mean time, exhibited the return of activity in this region, i.e. intrarenal reflux. Intrarenal reflux is an important risk factor in development of reflux nephropathy and its detection is of utmost importance in evaluating possible reflucting kidney damage and indicating children with high risk of renal scarring. We found the method of functional images of mean time to be more sensitive in detecting parenchymal changes than static scintigraphy with Tc-99m-DMSA, which was till now used for evaluation of kidney morphology. Likewise, we found the method of functional images of the mean time superior in detecting changes in upper urinary tract in comparison with excretory urography. The analysis of deconvolution numerical data exhibited the prolongation of parenchymal, renal pelvis and total kidney transit time in higher reflux degrees. These data contribute to better functional evaluation of reflucted kidney and point out the ones with great risk of renal scarring. We can conclude that careful analysis of each of the 6 functional images of the mean time and deconvolution of renographic curves with Tc-99m-DTPA contribute to early detection of children with vesicoureteral

Two radio aerosol preparations, TechneScan-DTPA (99mTc-DTPA, 40 mCi/3 ml; IPEN-CNEN, Sao Paulo, S P, Brazil) and TechneScan-DTPA/AEROSOL (99mTc-DTPA/A, 15 mCi/1.5 ml with 0.5 ml ethanol; Mallinckrodt Medical, St. Louis, M O, USA), were compared in pulmonary ventilation studies in terms of total radio counts and clearance after inhalation. An aerosol with ethanol is supposed to better distribute the radio particles in the lungs. Twenty normal non smoking volunteers (10 men and 10 women), mean age of 23.2 years (range: 20 to 35 years), were studied. Images were obtained immediately and 30, 60 and 90 min after inhalation. Total and regional counts were obtained and the clearance half-lives of both lungs were determined. There was no difference in total counts between the two types of radio aerosol at any time (mean of approx 188,00 cpm for male and female subjects at time zero in both aerosols). The highest count was obtained in the middle region of both lungs (P99m Tc-DTPA/A generated the highest output of radio aerosol. 99m Tc-DTPA with alcohol costs approximately five times more than the aerosol without alcohol. The present results show that either kind of aerosol may be adopted routinely for use in pulmonary examinations without affecting diagnosis. We suggest that the amount of 740 mBq (20 mCi) of 99mTc-DTPA in 1.5 ml saline can be used for routine examinations resulting in reduction of costs in pulmonary ventilation studies without diagnostic impairment. (author)

AIM: To evaluate the efficacy of a new nuclear imaging Infecton (Tc-99m ciprofioxacin) for the diagnosis of acute cholecystitis.METHODS: Sixteen patients thought to have acute cholecystitis were included in this study. The diagnosis of acute cholecystitis was made based on clinical symptoms and ultrasonographic and pathologic findings.RESULTS: The 16 patients were composed of 12 acute and 4 chronic cholecystitis patients. Twelve patients with acute cholecystitis were image-positive, including one false-positive. Four patients with chronic cholecystitis were image-negative, of whom three were true-negative.This nuclear imaging had a sensitivity of 91.7%, a specificity of 75%, a positive-predictive value of 91.7%,and a negative-predictive value of 75%.CONCLUSION: Tc-99m ciprofloxacin imaging is easy to perform and applicable for the diagnosis of acute cholecystitis.

The kinetics of myocardial imaging with Tc-99m methoxy methylpropyl isonitrile (MIBI) were studied in four healthy adult volunteers and ten patients with coronary artery disease and ischemia on exercise Tl-201 imaging. After administration of 4-10 mCi of Tc-99m MIBI, patients were reexcerised to the same level and imaged in the same manner at peak exercise levels and after rest. Low initial lung uptake, rapid biliary excretion, and good myocardial contrast without a change in heart rate or redistribution over 2 hours were seen on both exercise and rest injected studies. The data suggest the usefulness of Tc-99 MIBI in tomography, in the gated study of wall motion studies, in the assessment of acute infarction, and in the detection of coronary artery disease

Urinary tract infection (UTI) in children involving renal parenchyma, upper collecting system or bladder is one of the major causes for consideration in the diagnosis and management of paediatric nuclear medicine. Acute pyelonephritis is one of the prime causes of morbidity associated with urinary tract infection in children which can lead to progressive renal damage. Technetium-99m dimercaptosuccinic acid (DMSA) is used extensively for the assessment of UTI in paediatrics. The radiopharmaceutical preparation could be influenced by several factors, most of them are trivial, but invariably have severe impact on the quality of the scintiphotographs. This communication is mainly to highlight some of the issues related to 99mTc-DMSA preparation and the possible precautionary measures that need to be taken to obviate unwarranted problems. (author)

Tc-99m is used for diagnostic imaging in nuclear medicine through SPECT technique. It is obtained by the elution of 99Mo/99mTc generators. During the elution process 99Mo can be extracted becoming a radionuclidic impurity. One of the quality parameters of the eluate is the radionuclidic purity, MBT (molybdenum break through), defined as the ratio between 99Mo and 99mTc activities in the eluate. The North-American and European pharmacopoeias restrict the 99Mo content, respectively, in 0.015 e 0.1% and, according to the International Atomic Energy Agency (IAEA), the activity ratio at the moment of administration of the radiopharmaceutical to the patient, should not exceed 0.015%. In Brazil, the control of such parameter is not obliged in official regulations. Thus, the objective of this work is to evaluate the occurrence of 99Mo in 99mTc eluates. It was initially optimized a methodology to determine the activity of 99Mo in eluate samples. Efficiency curves were obtained for a NaI (Tl) 8'' x 4'' scintillation detector installed at the In Vivo Monitoring Laboratory (LABMIV-IRD). The methodology has been validated through the measurement of a 99Mo standard liquid source calibrated at the National Metrology Laboratory for Ionizing Radiation (LNMRI-IRD). The samples analyzed in this work were gently supplied by 5 Nuclear Medicine Clinics located in the city of Rio de Janeiro. The activities of 99mTc and 99Mo in those samples have been measured respectively at the clinics and at the LABMIV. By applying a standardized methodology, the ration between the activities were calculated. The results show that 147 out of 174 samples presented 99Mo activities above the minimum detectable activity of the technique. On the other hand, only 2 out of 147 samples surpassed the MBT limit suggested by the IAEA and have been detected in samples eluted from generators of 750 mCi. In one of the samples, eluted from a generator of 1000 mCi, the calculated MBT value was very close to the IAEA

A multi-center clinical study was performed in patinets with hepatic disorders to evaluate the clinical usefulness of 99mTc-DTPA-galactosyl serum albumin (99mTc-GSA), a new radiopharmaceutical which binds to asialoglycoprotein receptors on hepatocytes. The blood clearance and hepatic accumulation were evaluated on the basis of the dynamic data and serial hepatic images obtained for 20 min after 99mTc-GSA injection. The blood clearance and hepatic accumulation indices of 99mTc-GSA demonstrated the followings. In acute liver diseases, these indices reflected the clinical features of the disease and correlated with the laboratory test indices for the blood coagulation system. In chronic liver diseases, these indices changed in direct proportion to the progression of the hepatic disorder and correlated well with the conventional laboratory test results. In obstructive jaundice, these indices aided evaluation of the liver function despite the high serum bilirubin level. The indices reflected the change in the number of hepatocytes before and after hepatectomy. The scintigraphic findings with 99mTc-GSA permitted both functional and morphological evaluations of the liver and provide additional information compared with conventional liver scintigraphy. These results suggest that 99mTc-GSA scintigraphy may be useful for evaluating both the functional and morphology of the liver from a new viewpoint of receptor-mediated accumulation. (author)

A multi-center clinical study was performed in patinets with hepatic disorders to evaluate the clinical usefulness of {sup 99m}Tc-DTPA-galactosyl serum albumin ({sup 99m}Tc-GSA), a new radiopharmaceutical which binds to asialoglycoprotein receptors on hepatocytes. The blood clearance and hepatic accumulation were evaluated on the basis of the dynamic data and serial hepatic images obtained for 20 min after {sup 99m}Tc-GSA injection. The blood clearance and hepatic accumulation indices of {sup 99m}Tc-GSA demonstrated the followings. In acute liver diseases, these indices reflected the clinical features of the disease and correlated with the laboratory test indices for the blood coagulation system. In chronic liver diseases, these indices changed in direct proportion to the progression of the hepatic disorder and correlated well with the conventional laboratory test results. In obstructive jaundice, these indices aided evaluation of the liver function despite the high serum bilirubin level. The indices reflected the change in the number of hepatocytes before and after hepatectomy. The scintigraphic findings with {sup 99m}Tc-GSA permitted both functional and morphological evaluations of the liver and provide additional information compared with conventional liver scintigraphy. These results suggest that {sup 99m}Tc-GSA scintigraphy may be useful for evaluating both the functional and morphology of the liver from a new viewpoint of receptor-mediated accumulation. (author).

Of all radiopharmaceuticals, sup(99m)Tc-tetracycline has turned out to be the most efficient and to have a specific affinity for tumours. Due to its favourable physical properties, high doses can be given at relatively low radiation loads. Its pharmacological properties ensure that it is quickly eliminated from the rest of the body during enrichment in affinite tissue. Furthermore, it can be labelled at any time with an economical radionuclide. (GSE/AK)

Two hundred-two /sup 99m/Tc-DMSA renograms for urologic problems were evaluated. Some technical aspects of the examination and the value of the scintigraphic depth estimation are discussed. Pre- and postoperative uptake values in patients with renal surgery and sequential postoperative examinations are considered. The value of DMSA renograms in predicting recovery in obstructive uropathy and in deciding to opt for conservative therapy or nephrectomy is discussed.

Full Text Available Purpose: In this study, the team modeled the biodistribution and the efficiency of two 99m-technetium diethylene triamine penta acetate (99mTc-DTPA based radiopharmaceuticals.Methods: The first radiopharmaceutical (DTPA-CNESTEN is developed at the laboratories of the radiopharmaceutical production unit of the National Center for Nuclear Energy, Sciences and Technologies (CNESTEN-Morocco, and the second one is the commercial DTPA (DTPA-ref. Freeze-dried kits were successfully radiolabeled (radiochemical purity >95% with the 99m Tc. Then drugs were injected to male BALB/c mice. In each 2 min, 5 min, 15 min, 1 h and 2 h time points after injections we evaluate tissue’s distributions characteristics. At the end, an automatic modeling of the data were recorded from thyroid, blood and urinary excretion kinetics and biodistribution in mice using both DTPA kits. The study aimed to extract the parameters of the function used to fit the recorded data. Results and Conclusion: the team concluded that the biodistribution of 99mTc-DTPA can be modeled using a combination of two exponential parts. Moreover, the resultant plots showed that there is strong correlation between the formula found in literature and the one derived on the basis of the fit of data sets in this study. In addition, it was found that the biodistribution behaviors of the developed kit and the commercial one were very close. The obtained results suggest that the developed DTPA has practically the same kinetics as the commercial one.

Technetium 99m pertechnetate thyroid scans were performed on 57 infants referred for evaluation of suspected congenital hypothyroidism. Thyroid anatomy may be characterized by four general types, based on the scintigraphic findings: (1) normal size and location. (2) ectopic location. (3) no detectable thyroid activity. (4) normal location with increased size or uptake. There are diverse etiologies of congential hypothyroidism. Correlation of thyroid scintigraphy with blood T4 and TSH levels allows specific etiological diagnosis in the majority of cases of congential hypothyroidism.

We report the preclinical testing of a synthetic receptor-binding macromolecule, [99mTc]DTPA-mannosyl-dextran (36 kDa, 8 DTPA and 55 mannosyl units per dextran, KD = 0.12 nM), for sentinel node detection. Nonclinical safety studies included cardiac pharmacology safety studies, acute toxicology and pathology studies at 50 and 500 times the scaled human dose in both rats and rabbits after foot pad administration, and perivascular irritation studies in rabbits following intra-muscular administration at 100 and 1000 times the scaled human dose. Biodistribution studies in rabbits at 15 m, 1 h, and 3 h indicated that [99mTc]DTPA-mannosyl-dextran cleared the hind foot pad with a biological half-life of 2.21 ± 0.27 h. Other than mild hepatocyte hypertrophy in rabbits, no abnormalities in toxicology or pathology were found. Intravenous administration had no effect on survival, any clinical observations, electrocardiograms, or blood pressures. Intramuscular injection had no effect on survival, clinical observations, injection site observations, or injection site histopathology. The estimated absorbed radiation dose to the affected breast was 0.15 mGy/MBq and the effective dose was 1.06 x 10-2 mSv/MBq. This preclinical study demonstrates that [99mTc]DTPA-mannosyl-dextran has no toxicities and has an acceptable biodistribution and radiation dose

A 61 year-old woman underwent perfusion and inhalation lung scan for the evaluation of pulmonary thromboembolism. Tc-99m MAA perfusion lung scan showed multiple round hot spots in both lung fields. Tc-99m DTPA aerosol inhalation lung scan and chest radiography taken at the same time showed normal findings. A repeated perfusion lung scan taken 24 hours later demonstrated no abnormalities. Hot spots on perfusion lung scan can be caused by microsphere clumping due to faulty injection technique by radioactive embolization from upper extremity thrombophlebitis after injection. Focal hot spots can signify zones of atelectasis, where the hot spots probably represent a failure of hypoxic vasoconstriction. Artifactual hot spots due to microsphere clumping usually appear to be round and in peripheral location, and the lesions due to a loss of hypoxic vasoconstriction usually appear to be hot uptakes having linear borders. Although these artifactual hot spots have been well-known, we rarely encounter them. This report presents a case with artifactual hot spots due to microsphere clumping on Tc-99m MAA perfusion lung scan.

This paper addressed myocardial perfusion imaging providing a spatial dosimetric investigation of the 99mTc-radiopharmaceutical dose distribution at the myocardium. Radiological data manipulation was performed in order to create a computational voxel model of the heart. A set of images obtained by thoracic angiotomography and abdominal aorta was set up providing anatomic and functional information for heart modeling in SISCODES code. A homogeneous distribution of 99mTc was assumed into the cardiac muscle. Simulations of the transport of particles through the voxel and the interaction with the heart tissues were performed on the MCNP - Monte Carlo Code. The spatial dose distribution in the heart model is displayed as well as the dose versus volume histogram of the heart muscle. The present computational tools can generate spatial doses distribution in myocardial perfusion imaging. Specially, the dosimetry performed elucidates imparted dose distribution in the myocardial muscle per unit of injected 99m Tc activity, which can contribute to future deterministic effect investigations. (author)

The purpose of this study was to evaluate 99mTc-DTPA-HSA as an iliopelvic lymphoscintigraphic agent in 5 normal volunteers and 10 patients with metastases of malignant tumors (cancer, 9; and malignant lymphoma, 1) to the iliopelvic lymph nodes. The subjects underwent intradermal injection of 185 MBq of 99mTc-DTPA-HSA into digital web spaces of the feet. Massage was applied at the injection sites for 30 sec; the subjects then walked around for 2 min. Whole-body scintigrams were obtained 5 min after injection. The whole-body scanning speed was 20 cm/min. The tracer transport was prompt. Within 15 min after injection, the tracer reached the termination of the thoracic duct in all normal volunteers. Normal whole-body images of excellent quality delineated the lymph nodes and channels almost without background radioactivity. The images of 9 patients with metastases of cancer showed clearly the following abnormal patterns: a) obstruction of lymphatic system (5/9, 55.6%); b) absence of visualization of the thoracic duct (44.4%); c) decreased uptake in lymph nodes (88.9%); d) visualization of collateral circulation (44.4%); e) tracer extravasation into more proximal soft tissue (22.2%). The image in the patient with malignant lymphoma showed increased uptake in the enlarged lymph nodes in addition to the all abnormal findings mentioned above. We concluded that 99mTc-DTPA-HSA is an excellent radiopharmaceutical for iliopelvic lymphoscintigraphy. (author)

The purpose of this study was to evaluate 99mTc-DTPA-HSA lymphoscintigraphy in 5 normal volunteers and 8 patients with metastases of malignant tumors (cancer, 3: and malignant lymphoma, 5). The subjects underwent intradermal injection of 370 MBq of 99mTc-DTPA-HSA into digital web spaces of the feet and fingers and massage at the injection sites for 30 s. Whole-body and local scintigrams were obtained 5-15 min (early image) and 50-60 min (delayed image) after injection. The tracer transport was prompt. Within 15 min after injection the tracer reached the termination of the thoracic duct in all normal volunteers. Normal lymphoscintigrams were obtained images of excellent quality delineated the lymph nodes and channel almost without background radioactivity. The images of 8 patients with malignant tumors showed clearly the following abnormal patterns: (1) obstruction of lymphatic system and absence of visualization of thoracic duct, (2) decreased or high uptake in enlarged lymph nodes, (3) visualization of collateral circulation and tracer extravasation into more proximal soft tissue. We concluded that lymphoscintigraphy with 99mTc-DTPA-HSA was useful for detection of metastases to lymphatic system in the patients with malignant tumor. (author)

The diagnosis of osteomyelitis is a challenge for diagnostic imaging. Nuclear medicine procedures including white blood cell imaging have been successfully used for the identification of bone infections. This multinational, phase III clinical study in 22 European centres was undertaken to compare anti-granulocyte imaging using the murine IgG antibody besilesomab (Scintimun registered) with 99mTc-labelled white blood cells in patients with peripheral osteomyelitis. A total of 119 patients with suspected osteomyelitis of the peripheral skeleton received 99mTc-besilesomab and 99mTc-hexamethylpropyleneamine oxime (HMPAO)-labelled white blood cells (WBCs) in random order 2-4 days apart. Planar images were acquired at 4 and 24 h after injection. All scintigraphic images were interpreted in an off-site blinded read by three experienced physicians specialized in nuclear medicine, followed by a fourth blinded reader for adjudication. In addition, clinical follow-up information was collected and a final diagnosis was provided by the investigators and an independent truth panel. Safety data including levels of human anti-mouse antibodies (HAMA) and vital signs were recorded. The agreement in diagnosis across all three readers between Scintimun registered and 99mTc-HMPAO-labelled WBCs was 0.83 (lower limit of the 95% confidence interval 0.8). Using the final diagnosis of the local investigator as a reference, Scintimun registered had higher sensitivity than 99mTc-HMPAO-labelled WBCs (74.8 vs 59.0%) at slightly lower specificity (71.8 vs 79.5%, respectively). All parameters related to patient safety (laboratory data, vital signs) did not provide evidence of an elevated risk associated with the use of Scintimun registered except for two cases of transient hypotension. HAMA were detected in 16 of 116 patients after scan (13.8%). Scintimun registered imaging is accurate, efficacious and safe in the diagnosis of peripheral bone infections and provides comparable information to 99m

Diuretic sup(99m)Tc-DTPA renography assisted with furosemide was performed in 45 patients with obstructive uropathy and in 93 patients without obstruction. After hydration of 300 ml of water, 20 mg of furosemide (0.5 mg/kg in children) was injected intravenously 15 min. following 8 mCi of sup(99m)Tc-DTPA administration. To evaluate the effect of furosemide on urinary excretion, the excretion half time (T1/2) was obtained from the faster component on the sup(99m)Tc-DTPA excretion curve by two compartment analysis. T1/2 of upper limit was 2.5 min. 80% of patients with obstruction showed a prolonged T1/2. And 57% of patients with non-obstructive renal parenchymal damage also showed a prolonged T1/2. Therefore, it was difficult to separate the patients with obstructive uropathy from the patients with renal parenchymal damage by the results of prolonged T1/2 alone. However, it became quite helpful to separate these two different patients with prolonged T1/2 by evaluating serial dynamic images and renogram. Although frequently seen in patients without obstruction, ''socalled'' obstructive findings (radionuclide retention in the pelvicalyceal system and obstructive pattern on renogram) were rarely seen in the prolonged T1/2 patients with renal parenchymal damage. With the combined criteria of obstructive findings and prolonged T1/2, 71% of the patients with obstruction were correctly detected, and only 5% of false positives were observed among 93 patients without obstruction. It is suggested that diuretic renography can be useful to differentiate obstructive uropathy from non-obstructive disease in cases of obstructive findings on conventional sup(99m)Tc-DTPA renography. (J.P.N.)

The 111In and 99mTc standardization in a 4πβ-γ coincidence system is described. The 111In was produced by the reaction of 111Cd (p, n) 111In in the cyclotron. The 111In decays with a half life of 2.8 days by electron capture process, populating the excited levels of 111Cd, emitting two main gamma rays with energies of 171 keV and 245 keV. The 99mTc decay with a half life of 6.007 h for isomeric transition, from the radioactive decay of 99Mo. 111In standardization was carried out in a 4πβ-γ system, consisted of a gas flow proportional counter with 4π geometry coupled to a pair of NaI(Tl) scintillation counter with conventional electronics. The gamma window was set comprising the (171 keV + 245 keV) total absorption energy peaks. The choice of the window was based on the analysis of the extrapolation curves prediction, obtained by Monte Carlo simulation. The 99mTc standardization has been accomplished by the 4πβ-γ coincidence method using a thin window proportional counter in a 4π geometry coupled to a single NaI(Tl) scintillation counter. The beta efficiency was varied by electronic discrimination using a software coincidence counting system (SCS). Two windows were selected for the gamma channel: one at 140 keV gamma ray and the other at 20 keV X ray total absorption peaks. The result of the experimental activity of 111In two solutions agree with the results obtained by Monte Carlo simulation. The experimental activities of 99mTc for the two gamma windows are in agreement within the experimental uncertainty, indicating that the adopted methodology is adequate. (author)

This observational study was performed in order to assess the exercise-related incremental diagnostic accuracy of Tc-99m sestamibi myocardial perfusion imaging (MPI) in a hospital-based Australian population, and to assess the relative roles of exercise and pharmacological stress in myocardial perfusion imaging (MPI). Two hundred and eight adult patients who had both Tc-99m sestamibi myocardial perfusion imaging and coronary angiography within a median time of 16 weeks were studied. The diagnostic end-point was coronary artery lesions of ≥50% and >70% stenosis detected on angiography. Using receiver operating characteristic curve analysis, the overall diagnostic accuracy was calculated, as well as the comparative accuracies in patients who undertook various levels of exercise stress testing (n=130) and those who received pharmacological (dipyridamole) stress testing (n=78). The overall respective diagnostic accuracy of Tc-99m sestamibi MPI for the diagnosis of coronary artery disease (>70% stenosis) was 81% and 76% when using the diagnostic criterion of ≥50% stenosis. On direct comparison of perfusion defects with angiographic stenoses, the respective sensitivity and specificity for the detection of >70% stenosis in each coronary artery territory was 73% and 79%. Pharmacological MPI showed a significantly greater sensitivity for the detection of localised stenoses compared to the overall group who had exercise MPI performed. Consequently, exercise stress MPI showed significantly more false negative lesions compared to dipyridamole stress imaging (p<0.003). However, a large proportion of patients were unable to perform to adequate exercise levels in this patient sample. We conclude that Tc-99m sestamibi myocardial perfusion imaging is an accurate non-invasive test for the diagnosis of coronary artery disease. Where any doubt exists as to the patient's ability to achieve exercise levels at or above 85% of the predicted value for age and gender, pharmacological

DTPA is also a good method for the relative renal function evaluation when compared to Tc 99m DMSA scan. Although Tc 99m DMSA is the most reliable method for the calculation of relative renal function, Tc 99m DTPA can be another choice for the calculation of relative renal function without a complementary DMSA scan particularly in patients who require renogram curve and GFR calculations. (MIRT 2011; 20:14-8

Process validation provides the best platform in identifying potential problems in the actual radiopharmaceuticals manufacturing work. The purpose of this paper is to present experience in performing process validation for the manufacturing of Tc-99m generator at Nuclear Malaysia. Process validation for the manufacturing of Tc-99m generator was done by performing four try runs, between October 2006 to April 2007. It was done using saline instead of the actual product. Each try run took four days to complete. On day 1, clean room was cleaned and disinfected. On day 2, activity of washing and sterilization of utensils, columns, rubber stoppers and aluminium caps was carried out. On day 3, preparation of white top, alumina packed column and mixing solutions was performed. Apparatus was also sent for sterilizing test. On day 4, the actual production day of the try run by impregnating column with sterile saline was performed. Prior to the manufacturing activities, particle counts measurement and area clearance were performed to ensure that the temperature and humidity of the clean room are suitable for the production work. Settle plates were placed at the identified positions including in the Hot Cell. Personnel's finger print was performed before and after production work by using touch plates. After completion of try run, elution from the generators that been manufactured, settle and touch plates were sent to quality control unit for the microbiological test. It took fourteen days to get the test results. The first try run was failed, which may be due to insufficient of proper arrangement/preparation of work. It may also due to problem of cleaning/disinfection of clean room, which may not be done properly. The further three consecutive try runs meet all the specifications including the sterility test, endotoxin test and finger prints. It shows that the manufacturing of Tc-99m generator at Nuclear Malaysia is validated and ready for the active run. (Author)

Introduction: Aptamers are oligonucleotides that have high affinity and specificity for their molecular targets which are emerging as a new class of molecules for radiopharmaceuticals development. In this study, aptamers selected to Staphylococcus aureus were evaluated for bacterial infection identification. Methods: Anti S. aureus aptamers were labeled with 99mTc by the direct method. The radiolabel yield and complex stability were assessed by thin-layer chromatography (TLC). Three groups of Swiss mice containing 6 animals each were used. The first group was infected intramuscularly in the right thigh with S. aureus. The second group was infected in the same way with C. albicans and the third group was injected with zymosan to induce aseptic inflammation. After 24 h, radiolabeled aptamers (22.2 MBq) were injected by the tail vein. The mice were euthanized 4 h post injection and tissue sample activities measured in a gamma counter. Results: The 99mTc labeled aptamers were stable in saline, plasma and cystein excess. Radiolabeled aptamers showed increased uptake in the kidneys for all groups indicating a main renal excretion, which is consistent with the hydrophilic nature and small size of aptamers. The radiopharmaceutical showed rapid blood clearance indicated by a reduced dose (% ID/g) in the blood. The biodistribution showed that aptamers were able to identify the infection foci caused by S. aureus displaying a target/non-target ratio of 4.0 ± 0.5. This ratio for mice infected with C. albicans was 2.0 ± 0.4 while for mice with aseptic inflammation was 1.2 ± 0.2. Histology confirmed the presence of infection in groups 1 and 2, and inflammation in group 3. Conclusions: The biodistibution study demonstrated a statistically higher uptake in the S. aureus foci relative to inflammation and C. albicans infected areas. These results highlight the potential of aptamers labeled directly with 99mTc for bacterial infection diagnosis by scintigraphy

The biologic behavior of human polyclonal immunoglobulin (IgG) radiolabeled with technetium-99m (99mTc) by a novel method, via a nicotinyl hydrazine derivative, was evaluated in rats. Technetium-99m- and indium-111-IgG were co-administered to normal rats and biodistribution was determined at 2, 6, and 16 hr. The inflammation imaging properties of the two reagents were compared in rats with deep-thigh infection due to Escherichia coli. Blood clearance of both antibody preparations was well described by a bi-exponential function: (99mTc-IgG: t1/2 = 3.82 +/- 0.89 and 57.52 +/- 1.70 hr. 111In-IgG: 3.93 +/- 0.117 and 40.71 +/- 1.26 hr). Biodistributions in the solid organs were similar, however, small but statistically significant differences were detected: 99mTc-IgG greater than 111In-IgG in lung, liver, and spleen; 99mTc-IgG less than 111In-IgG in kidney and skeletal muscle (p less than 0.01). At all three imaging times, target-to-background ratio and percent residual activity for the two compounds were remarkably similar. These studies establish that human polyclonal IgG labeled with 99mTc via a nicotinyl hydrazine modified intermediate is equivalent to 111In-IgG for imaging focal sites of infection in experimental animals

When pathologically externalized, phosphatidylethanolamine (PE) is a potential surrogate marker for detecting tissue injuries. 99mTc-labeled duramycin is a peptide-based imaging agent that binds PE with high affinity and specificity. The goal of the current study was to investigate the clearance kinetics of 99mTc-labeled duramycin in a large animal model (normal pigs) and to assess its uptake in the heart using a pig model of myocardial ischemia–reperfusion injury. Methods: The clearance and distribution of intravenously injected 99mTc-duramycin were characterized in sham-operated animals (n = 5). In a closed chest model of myocardial ischemia, coronary occlusion was induced by balloon angioplasty (n = 9). 99mTc-duramycin (10–15 mCi) was injected intravenously at 1 hour after reperfusion. SPECT/CT was acquired at 1 and 3 hours after injection. Cardiac tissues were analyzed for changes associated with acute cellular injuries. Autoradiography and gamma counting were used to determine radioactivity uptake. For the remaining animals, 99mTc-tetrafosamin scan was performed on the second day to identify the infarct site. Results: Intravenously injected 99mTc-duramycin cleared from circulation predominantly via the renal/urinary tract with an α-phase half-life of 3.6 ± 0.3 minutes and β-phase half-life of 179.9 ± 64.7 minutes. In control animals, the ratios between normal heart and lung were 1.76 ± 0.21, 1.66 ± 0.22, 1.50 ± 0.20 and 1.75 ± 0.31 at 0.5, 1, 2 and 3 hours post-injection, respectively. The ratios between normal heart and liver were 0.88 ± 0.13, 0.80 ± 0.13, 0.82 ± 0.19 and 0.88 ± 0.14. In vivo visualization of focal radioactivity uptake in the ischemic heart was attainable as early as 30 min post-injection. The in vivo ischemic-to-normal uptake ratios were 3.57 ± 0.74 and 3.69 ± 0.91 at 1 and 3 hours post-injection, respectively. Ischemic-to-lung ratios were 4.89 ± 0.85 and 4.93 ± 0.57; and ischemic-to-liver ratios were 2.05 ± 0.30 to 3

Full Text Available Abstract Background Renal scintigraphy using 99mTc-mercaptoacetyltriglycine (99mTc-MAG3 is widely used for the assessment of renal function in humans. However, the application of this method to animal models of renal disease is currently limited, especially in rodents. Here, we have applied 99mTc-MAG3 renal scintigraphy to a mouse model of unilateral ureteral obstruction (UUO and evaluated its utility in studying obstructive renal disease. Methods UUO mice were generated by complete ligation of the left ureter. Sham-operated mice were used as a control. Renal function was investigated on days 0, 1, 3, and 6 post-surgery using dynamic planar imaging of 99mTc-MAG3 activity following retro-orbital injection. Time-activity curves (TACs were produced for individual kidneys and renal function was assessed by 1 the slope of initial 99mTc-MAG3 uptake (SIU, which is related to renal perfusion; 2 peak activity; and 3 the time-to-peak (TTP. The parameters of tubular excretion were not evaluated in this study as 99mTc-MAG3 is not excreted from UUO kidneys. Results Compared to sham-operated mice, SIU was remarkably (>60% reduced in UUO kidneys at day 1 post surgery and the TACs plateaued, indicating that 99mTc-MAG3 is not excreted in these kidneys. The plateau activity in UUO kidneys was relatively low (~40% of sham kidney’s peak activity as early as day1 post surgery, demonstrating that uptake of 99mTc-MAG3 is rapidly reduced in UUO kidneys. The time to plateau in UUO kidneys exceeded 200 sec, suggesting that 99mTc-MAG3 is slowly up-taken in these kidneys. These changes advanced as the disease progressed. SIU, peak activity and TTPs were minimally changed in contra-lateral kidneys during the study period. Conclusions Our data demonstrate that renal uptake of 99mTc-MAG3 is remarkably and rapidly reduced in UUO kidneys, while the changes are minimal in contra-lateral kidneys. The parametric analysis of TACs suggested that renal perfusion as well as tubular

flow (rCBF) was measured tomographically with the 133Xe inhalation technique. We applied a three-compartment kinetic model and algorithms modified from a previous analysis of 99mTc d,l-hexamethylpropyleneamine oxide (HM-PAO) kinetics. The bicisate brain uptake and retention curve was very similar to...... that of HM-PAO, and it can be described by a triexponential function including an initial steep component representing the vascular transmitted spike, a second less steep component representing back-diffusion from brain tissue to blood, and a third, very slow component, representing the very slow loss...

The usefulness of sup(99m)Tc-Hydroxymethylene Diphosphonate (HMDP), a new skeletal scintigraphy agent, to detect the bone lesions, was investigated by comparing with sup(99m)Tc-Methylene Diphosphonate (MDP). No significant difference in blood clearance between HMDP and MDP was observed in 5 healthy volunteers. Any difference was not seen in the urinary excretion studies between these two agents. Inorder to estimate the uptake of these agents by bone, the count ratio of normal bone to soft tissue was obtained in 22 cases with HMDP and 23 with MDP by scintimetry. This data suggested that HMDP bone to soft tissue ratio was significantly higher than that of MDP. Although this ratio of HMDP was not significantly higher than that of MDP before first 1 hour after administration, the former became gradually higher than the latter, and difference was significant 2 hour after administration. Overall, HMDP image was judged to be slightly better than MDP in qualitatively grading by three independent observers. From these results it is concluded that HMDP is a useful skeletal imaging agent. (author)

The rate of clearance (K value) of 99mTc tin colloid in the liver differentiates normal subjects from liver cirrhosis patients; so 99mTc tin colloid is as useful as 198Au colloid as a marker of liver function. There are several reports concerning volume estimation using liver scintigraphy. Our original method was devised to measure the effective liver volume by scintigraphy. By combining the K value with effective liver volume, a predictive index was obtained in order to predict the residual liver function before hepatic resection. The index in 24 patients with liver diseases was investigated before hepatic resection. Three of them died due to hepatic failure after hepatic resection. The indices were between 0.40 and 0.45 in two of these three patients and 0.338 in one. Among the patients without hepatic failure, the indices showed more than 0.45 in 19 patients and between 0.40 and 0.45 in two. These results indicate that the limitation of hepatic resection is between 0.40 and 0.45 of the predictive index. (author)

A pyridoxine (vitamin B6)-deficient diet in rats was used as a model of early renal lithiasis to find out if stone-formers could be identified from control animals by differences in the biodistribution of Tc-99m MDP. The mean renal uptake of this agent at 3 hours was about 70% higher in test animals than in controls, but there was considerable overlap between the upper limits of the normal range and lower values in stone-formers. If these results were valid for humans, the metabolic abnormality in males with early stone-forming disease could not be identified with certainty by in vivo measurements of Tc-99m MDP renal uptake alone. However, the skeletal uptake of MDP in the stone-forming animals was depressed by 28 to 35%, compared with control rats. Consequently, the renal to skeletal MDP concentration ratio was invariably elevated in stone-formers beyond the 95 percentile normal range. Unexpectedly, 76% of the pyridoxine-deficient animals had a higher accumulation of MDP in the myocardium than the upper limit of the normal range. The pyridoxine-deficient diet induced no remarkable early changes in the biodistribution or renal clearance of I-131 Hippuran

Diisopropyl-IDA TC 99m imaging studies were performed in 11 normal subjects in both the fasting and postprandial states. In 5- to 60-minute analog images obtained in both fasting and postprandial studies, the cardiac blood pool was almost never seen, renal pelvic radioactivity was commonly seen, the extrahepatic biliary tract was always seen, and the left hepatic duct was always more prominent than the right hepatic duct. The billiary tract was visualized by ten minutes in nine of 11 fasting studies and 10 of 11 postprandial studies. The gallbladder was visualized in all eleven fasting studies, but in only four postprandial studies (p<0.05). The zero- to sixty-minute digital data indicated a greater hepatocyte clearance, an earlier time of peak parenchymal radioactivity, and a faster parenchymal washout in the postprandial studies compared with fasting studies (p<0.05). Approximately nine percent of the injected dose was recovered in the urine during the first three hours in fasting and postprandial studies. The normal diisopropyl-IDA Tc 99m study in the fasting and postprandial states is defined; significant differences exist between the two states

This study aimed to evaluate if the splenectomy alters the biodistribution of 99mTc-DMSA and renal function in Wistar rats. The animals were separated in the groups: splenectomy (n = 6) and control (n = 6). After splenectomy (15 days), the administration of 0.1 ml of 99mTc-DMSA IV (0.48 MBq) was carried out. Thirty minutes later, kidney, heart, lung, thyroid, stomach, bladder and femur and samples of blood were isolated. The organs were weighed, counted and the percentage of radioactivity /g (%ATI/g) determined. Serum urea and creatinine, hematocrit, leukocytes and platelets were measured. Statistics by t test (p<0.05) was done. There was a significant reduction in %ATI/g in kidney and blood (p<0.05) of splenectomized animals, a significant increase (p<0.05) of urea (88.8 ± 18.6 mg/dL) and creatinine (0.56 ± 0.08 mg/dL), compared to the controls (51.5±1.6, 0.37±0.02 mg/dL, respectively), as well as increase in platelets and leucocytes, and hematocrit reduction. The analysis of the results indicates that in rats, splenectomy seems to alter the renal function and the uptake of 99mTc-DMSA. (author)

This study aimed to evaluate if the splenectomy alters the biodistribution of 99mTc-DMSA and renal function in Wistar rats. The animals were separated in the groups: splenectomy (n = 6) and control (n = 6). After splenectomy (15 days), the administration of 0.1 ml of 99mTc-DMSA IV (0.48 MBq) was carried out. Thirty minutes later, kidney, heart, lung, thyroid, stomach, bladder and femur and samples of blood were isolated. The organs were weighed, counted and the percentage of radioactivity /g (%ATI/g) determined. Serum urea and creatinine, hematocrit, leukocytes and platelets were measured. Statistics by t test (p<0.05) was done. There was a significant reduction in %ATI/g in kidney and blood (p<0.05) of splenectomized animals, a significant increase (p<0.05) of urea (88.8 {+-} 18.6 mg/dL) and creatinine (0.56 {+-} 0.08 mg/dL), compared to the controls (51.5{+-}1.6, 0.37{+-}0.02 mg/dL, respectively), as well as increase in platelets and leucocytes, and hematocrit reduction. The analysis of the results indicates that in rats, splenectomy seems to alter the renal function and the uptake of 99mTc-DMSA. (author)

A digital simulation method for quantitative evaluation of renal function by using sup(99m)Tc-DMSA was proposed. The ultimate renal DMSA uptake rate, saturation time, and percent renal blood volume were calculated by this method, and its clinical usefulness was evaluated. This analytical method was thought to be reliable from the fact that calculated renal uptake rates showed a significant correlation with observed values after 2hrs' administration. Furthermore, calculated renal uptake rates were significantly correlated with the values of renal plasma flow and creatinine clearance. In the cases with obstructive uropathy, calculated renal uptake rate, saturation time, and percent renal blood volume were thought to reflect the grade and the feature of the disease. From these results, my proposed method was considered to be clinically useful as a quantitative renal function test.

In recent years it became possible to study liver function and bile excretion by use of 99mTc-preparations of iminodiacetic acid. The primary intent of the work was to standardize the technical conditions for examination on gamma camera, for quantitative assessment of the diagnostic information being obtained in 20 normal subjects, which is essential for adequate interpretation of the results in patients with hepato-biliary disorders. It was found that the normal clearance of the radiodye was 2,67±0,89 min, the liver maximal deposition time was 10,30±1,69 min, the deposition index - 6,49±1,5, the retention index - 0,48±0,28, the gall bladder mean apprerance time - 20,14±3,12 min, the intestine mean appearance time - 21,23±11,25 min

30 cases of normal 99mTc-PMT hepatobiliary scintigraphy with deconvolution analysis was reported. From ordinary time-activity curve (T-A curve) of liver, the Tmax, T1/2max as well as the retaining rate in 60 min was determined. By calculating the transfer function, minimum (min) mean and maximum (max) transit time (TT) were further measured, and from above data the functional image of various regional phases of the liver thus obtained. At the same time, the blood retaining rate in 5 min and the effective hepatic blood flow were also measured. Transfer function was calculated by the T-A curve with direct bolus injection into the main hepatic artery. Thereby, it is more sensitive and accurate in reflecting the hepatic excretory function. The various normal parameters of hepato-biliary function obtained were useful for the comparative study of hepatic diseases

In contrast to 201TlCl, 99mTc-sestamibi shows very slow myocardial clearance after its initial myocardial uptake. In the present study, myocardial washout of 99mTc-sestamibi was calculated in patients with non-ischemic chronic heart failure (CHF) and compared with biventricular parameters obtained from first-pass and ECG-gated myocardial perfusion SPECT data. After administration of 99mTc-sestamibi, 25 patients with CHF and 8 normal controls (NC) were examined by ECG-gated myocardial perfusion SPECT and planar data acquisition in the early and delayed (interval of 3 hours) phase. Left ventricular ejection fraction (LVEF, %), peak filling rate (PFR, sec-1), end-diastolic volume (LVEDV, ml) and end-systolic volume (LVESV, ml) were automatically calculated from the ECG-gated SPECT data. Myocardial washout rates over 3 hours were calculated from the early and delayed planar images. Myocardial washout rates in the CHF group (39.6±5.2%) were significantly higher than those in the NC group (31.2±5.5%, p99mTc-sestamibi is considered to be a novel marker for the diagnosis of myocardial damage in patients with chronic heart failure. (author)

Introduction: Hypoxia plays a negative role in the clinical management of cancer. Detection of hypoxic status of a cancer is important for selecting patients for hypoxia directed therapy. Though [18 F]fluoromisonidazole ([18 F]FMISO), a PET radiopharmaceutical, is presently being used in the clinic for the detection of hypoxia, considering the logistical advantages of 99mTc and wider availability of SPECT scanners, a radiopharmaceutical based on this isotope may find wider applicability. Methods: Nine nitroimidazole (2-, 4- and 5-nitroimidazole) ligands were synthesized and radiolabeled using [99mTc(CO)3(H2O)3]+ precursor to obtain a group of complexes possessing different single electron reduction potential (SERP), overall charge and lipophilicity, the three attributes which decide the efficacy of the complex to detect hypoxic cells in vivo. The nitroimidazole-99mTc(CO)3 complexes as well as [18 F]FMISO were evaluated in fibrosarcoma tumor bearing mice. Results: The 99mTc(CO)3 complexes of nitroimidazole iminodiacetic acid (IDA) showed better tumor uptake and retention than nitroimidazole diethylenetriamine (DETA) and nitroimidazole aminoethylglycine (AEG) complexes. Tumor uptake observed with [18 F]FMISO was higher than any of the nitroimidazole-IDA- 99mTc(CO)3 complexes. However, [18 F]FMISO clearance from tumor was found to be faster compared to 2-nitroimidazole-IDA-99mTc(CO)3 complex. Observed tumor uptake and retention of the radiotracers evaluated could be correlated to its blood clearance pattern and SERP. Conclusions: Results of the present study indicated that uptake of the radiotracer in tumor is closely associated with its rate of clearance from blood. The study also indicated that along with SERP, clearance of radiotracer from blood (net effect of charge and lipophilicity) is a critical factor which decides the in vivo efficacy of the hypoxia detecting radiopharmaceutical

99mTc elution yield is an important quality parameter of 99mTc generator. 99mTc elution yield can be measured by the methods such as the quantitative analysis, the γ spectrometer analysis and the shield analysis. The shield analysis is used to measure 99mTc elution yield considering the process and structure of gel generator. The principle and method to measure 99mTc elution yield of 99mTc gel generator are introduced, and the measured result of 99mTc elution yield are given

We have studied two types of targets zirconium-molybdate (ZrMo) and titanium-molybdate (TiMo) prepared by precipitating reaction between ammonium-molybdate and zirconium-chloride or titanium-chloride solutions, respectively. Other types of targets were also prepared by co-precipitating ZrMo or TiMo with hydrous manganese-dioxide, hydrous silica, and hydrous titanium-dioxide or by impregnated ZrMo or TiMo with Iodate anions. The results on extraction of Tc-99m from neutron irradiated TiMo solid phase using solvents such as MEK, aceton, ethylic ether, chloroform, etc showed that separation yield (SY) of Tc-99m in case of aceton extraction was from 70% to 80% and in other cases non higher than 40%. The Tc-99m elution curves and column kinetic in case of aceton extraction (after evaporation of aceton and recovery of Tc-99m in 0,9% NaCl solution) was superior than in case chromatographic generator using saline eluant. As result obtained, two types of generators were successfully prepared and put into use: Chromatographic generator using titanium-molybdate target as packing material and saline as eluant. Solid-solvent extraction 99mTc generator using titanium-molybdate target (as solid phase) and aceton as extracting solvent. (author)

We have studied two types of targets zirconium-molybdate (ZrMo) and titanium-molybdate (TiMo) prepared by precipitating reaction between ammonium-molybdate and zirconium-chloride or titanium-chloride solutions, respectively. Other types of targets were also prepared by co-precipitating ZrMo or TiMo with hydrous manganese-dioxide, hydrous silica, and hydrous titanium-dioxide or by impregnated ZrMo or TiMo with Iodate anions. The results on extraction of Tc-99m from neutron irradiated TiMo solid phase using solvents such as MEK, aceton, ethylic ether, chloroform, etc showed that separation yield (SY) of Tc-99m in case of aceton extraction was from 70% to 80% and in other cases non higher than 40%. The Tc-99m elution curves and column kinetic in case of aceton extraction (after evaporation of aceton and recovery of Tc-99m in 0,9% NaCl solution) was superior than in case chromatographic generator using saline eluant. As result obtained, two types of generators were successfully prepared and put into use: Chromatographic generator using titanium-molybdate target as packing material and saline as eluant. Solid-solvent extraction {sup 99m}Tc generator using titanium-molybdate target (as solid phase) and aceton as extracting solvent. (author)

Histological and morphometric evaluation of ocular inflammation is difficult, particularly when there is extensive ocular involvement with abscess formation and necrosis. A quantitative imaging procedure applicable to humans would be important clinically. To establish such a procedure, turpentine-induced ocular inflammation was obtained by subconjunctival injection in the right eye of 55 rabbits. The left eye was used as control and injected with a volume of saline equal to the volume of turpentine in the right eye. Volumes of turpentine or saline were 0.02, 0.04, 0.06, 0.2 and 0.6 ml, and the rabbits were divided into groups 1-5, according to these volumes. Imaging was performed 48 h after turpentine injection and 6 h after intravenous injection of 10 mCi of technetium 99m glucoheptonate (99mTc-GH). An inflammatory reaction index (IRI), defined as the ratio of counts of the right eye divided by counts of the left eye, was used. IRIs were proportional to the degree of inflammation and allowed the distinction of 3 subgroups: One represented by group 4, one by group 5 and one by groups 1, 2 and 3. This method of quantification of ocular inflammatory processes using 99mTc-GH is original, rapid, non-invasive, reproducible and safe, although unable to differentiate inflammatory processes caused by doses of turpentine which are very small and close to each other. It is conceivable that its application to humans will bring new insight into the ocular inflammatory process and response to therapy. (orig.)

Aims: Technetium-99-MIBI myocardial perfusion scintigraphy is a routinely employed nuclear medicine procedure. This study was carried out to get additional information in terms of Lung-heart ratio (LHR), Right ventricular index (RVI) by computer assisted quantification analysis of this procedure. Material and Methods: Fifty diagnosed cases of coronary artery disease (CAD) underwent 99mTc-MIBI planar studies at stress and rest. A group of 15 subjects with low pre-test likelihood of CAD and normal exercise and rest 99mTc-MIBI images was used as control. LHR was calculated from the static images in the anterior view. A circular region of interest (ROI) of about 8 pixel in diameter was selected in left lung area at maximal count density as assessed visually. Similar ROI was drawn on left ventricular wall at maximal count density area, as assessed visually. Ratio of the counts in the lung ROI to the counts in the myocardial ROI was expressed as Lung Heart ratio or 'lung index. LHR = Average counts in Lung ROI/Average counts in Left Myocardial ROI. Right ventricular index (RVI) was determined from the static images in LAO 450 views. ROIs were drawn on the right ventricle (RV) with maximal counts and on the left ventricle (LV) with maximal counts as assessed visually. The ratio of the counts in the two ROIs gave the right ventricular index. RVI = Average counts in RV ROI/ Average counts in LV ROI. Results: A close correlation was noted in the findings of three independent observers. In patients or coronary artery disease group (CAD Group), stress was induced by treadmill exercise or dipyridamole infusion. The CAD Group showed higher LHR at stress and at rest than controls. Student's t-test comparison of patients versus controls. p99mTc-MIBI myocardial perfusion images provides reproducible and clinically useful information regarding left ventricular function in CAD patients

Papers on deposition pattern analyses of radioaerosol lung scans are few and not easy to interpret as there is a general lack of technical standardization and the number of patients studied is not large. Moreover these reports have been generally obtained with non-hydrosoluble radioaerosols. In the present study 43 patients underwent conventional pulmonary function testing and lung scanning using small droplet (equal or less than 2 microns) polydisperse sup(99m)Tc-DTPA radioaerosol produced with the ''Settling Bag System'' Medi 400 (Sorin). The scans were analysed by two methods: 1) a semiquantitative method proposed by Taplin (SQT); 2) an original simpler semiquantitative method (SQM). Correlations of SQT and SQM with FEV1 and MEF75 resulted highly significant (p<0,001). SQM proved to be superior so SQT as far as reproducibility is concerned. The following conclusions can be drawn: 1) small particle sup(99m)Tc-DTPA aerosol can be easily and cheaply produced by a commercial device; 2) such a radioaerosol is well suited for the evaluation of small and large airways patency, as reflected by MEF75 and FEV1 respectively, with a diagnostic yield comparable to non-hydrosoluble radioaerosols; 3) the original semiquantitative description of the deposition pattern proposed and validated in this study is quite easy to implement and it yields a high correlation with pulmonary function tests; moreover such an approach does not require digital data processing; 4) the sensitivity of sup(99m)Tc-DTPA for the diagnosis of bronchial obstruction is very high and superior to routine pulmonary function tests; in addition the ventilation scan allows the topographical localization of the obstruction themselves

Good manufacturing practices specify that a well-type scintillation NaI(Tl) crystal detector has to be validated in order to detect radioactivity from any radiopharmaceutical used to obtain radiopharmacokinetic parameters. A 5 cm well-type NaI(Tl) scintillation detector was coupled to a multi-channel analyzer centered at the 140 keV 99mTc peak with a 20% window. The area represents counts per minute (cpm). All the net cpm were decay corrected. The activity source was 99mTc-glucarate developed as an imaging agent for acute myocardial infarction. Wistar rats were injected in a tail vein with 0.1 ml (3.7 MBq) of 99mTc-glucarate solution and 13 blood samples were taken. The cpm were the input data for the WINNONLN program which calculates radiopharmacokinetic parameters. The detector's efficiency for 99mTc was 15.03% and the sensitivity 1.12 kBq/ml in plasma. The response was linear between 0.31-14.3 kBq/ml of 99mTc-glucarate. The maximum assay variation coefficient was 2.79 and recovery of 99mTc-glucarate in plasma was 99.8% ± 0.2%. LOD was 0.31 kBq and LOQ 1.12 kBq in plasma samples. 99mTc-glucarate follows a two-compartment model of distribution with Vd of 21.74 ml ± 2.71 ml; a Vdss of 74.36 ml ± 12.67 ml; t1/2α 0.74 h ± 0.19 h; t1/2β 18.98 h ± 4.36 h; AUC = 32.75 μCi/min x ml ± 3.73 μCi/min x ml; MRT 24.35 h ± 5.51 h and total clearance 3.05 ml/h ±0.35 ml/h. The well-type detector fulfills the quality system requirements and the radiopharmacokinetic parameters for 99mTc-glucarate in rats are reliable. (author)

The reliability and applicability of the preparation of the three, for nuclear medicine very important, 99mTc-radiopharmaceuticals from the inactive (technetium-cold) kit solutions were tested. Each examined commercial kit was dissolved in saline (0.9 % NaCl). The conditions of the storage of the inactive kit solutions till labeling were examined. The main problem is the stablity of the reductant stannous ions which is very difficult to predict. To stabilize and ensure a good quality of the l...

It has been known that hyperfixation of Tc-99m ECD (HF) is not shown in subacute cerebral infarction because the brain distribution of Tc-99m ECD reflects not only perfusion but also the metabolic status of brain tissue. However, we observed several cases with HF in the subacute pure cortical infarction. To find out the cause of HF in subacute cortical infarction. We assessed the difference in associated cerebral hemodynamics and clinical findings between the subacute cortical infarctions with and without HF. We reviewed 16 patients (63.8{+-}8.6 yr, M/F: 15/1) with pure cortical infarction not involving adjacent subcortical white matter on MRI. All patients underwent acetazolamide stress brain perfusion SPECT using Tc-99m ECD and MRI at subacute period (7.3{+-}4.4 days from ictus). Uptake of Tc-99m ECD in infarcted cortex was assessed visually comparing the contralateral side. To assess the difference in associate clinical findings between the infarctions with and without HF, rCVR of the cerebral territory including infarcted cortex, extent of Gd-enhancement on MRI. Intervals between SPECT and ictus, and the presence of associated ICA stenosis were evaluated. Infarctions were focal (n=8) or multifocal (n=8) and located in frontoparietal cortices on MRI. Twelve patients were accompanied with ipsilateral ICA stenosis. Resting SPECT showed increased cortical uptake (=HF) in 7 patients and decreased in 9. rCVR of the MCA territory was preserved in all of the 7 patients with HF, compared with 4 of the 9 patients without HF (p=0.03). Gd-enhancement was minimal in all of the 7 patients with HF, compared with of the 0 patients without HF (p=0.03). Presence of ipsilateral ICA stenosis and intervals from ictus were not different (p>0.1) Subacute cerebral cortical infarction with HF was more frequently associated with preserved rCVR and minimal destruction of the blood-brain barrier than that without HF. Our findings suggest that HF may result from luxury perfusion of

A simple, accurate test with no morbidity and effective for the detection of urinary tract obstruction in patients with normal and impaired renal function would be of significant clinical use. The ability of 99m technetium diethylenetriaminepentaacetic acid to detect the presence or absence of obstruction is evaluated. Obstructions were defined as abnormal retention of activity in the collecting system persisting in the delayed images. Diethylentriaminepentaacetic acid identified correctly 13 of 13 patients proved to have obstruction and 17 of 18 without obstruction. These data indicate a sensitivity of 100 percent, specificity of 94 percent and accuracy of 97 percent

A simple, accurate test with no morbidity and effective for the detection of urinary tract obstruction in patients with normal and impaired renal function would be of significant clinical use. The ability of 99m technetium diethylenetriaminepentaacetic acid to detect the presence or absence of obstruction is evaluated. Obstructions were defined as abnormal retention of activity in the collecting system persisting in the delayed images. Diethylentriaminepentaacetic acid identified correctly 13 of 13 patients proved to have obstruction and 17 of 18 without obstruction. These data indicate a sensitivity of 100 percent, specificity of 94 percent and accuracy of 97 percent.

Technetium 99m pertechnetate thyroid scans were performed on 57 infants referred for evaluation of suspected congenital hypothyroidism. Thyroid anatomy may be characterized by four general types, based on the scintigraphic findings: (1) normal size and location. (2) ectopic location. (3) no detectable thyroid activity. (4) normal location with increased size or uptake. There are diverse etiologies of congential hypothyroidism. Correlation of thyroid scintigraphy with blood T4 and TSH levels allows specific etiological diagnosis in the majority of cases of congential hypothyroidism. (orig.)

Goiters are rarely palpable in infants with congenital hypothyroidism except in the case of maternal ingestion of iodide. The presence or absence of glandular tissue is, however, important for genetic and prognostic counseling and for acceleration of diagnosis in other affected siblings. The detection of thyroid tissue by /sup 99m/Tc pertechnetate scans in a significant number of our patients heretofore considered athyreotic establishes that physical findings and traditional laboratory data are not adequate to determine whether or not thyroid tissue is present

The major clinical use of ventilation perfusion scintigraphy is for the diagnosis of pulmonary embolism (PE). Accurate diagnosis of PE is essential since effective treatment if available. The scintigraphic characteristic of PE are segmental perfusion defects in lung that is normally ventilated. The inherent shortcoming of perfusion scintigraphy is its lack of specificity. Combining a ventilation study with perfusion imaging improves the diagnostic specificity of lungs scintigraphy. This article describes clinical use of simple same day ventilation and perfusion imaging technique. The technique is based on a low dose ventilation procedure using 99m Tc labelled aerosol immediately followed by a standard dose perfusion procedure. (author)

Starting from routine renal clearance measurements in a partially shielded whole-body counter, generally applicable algorithms were developed empirically which permit the reconstruction of the total course of retention up to 28 min p.i. from e.g. the 12 min and 24 min values only. By formal differentiation the instanteneous slope of the decline in retention and thus the renal clearance can be calculated employing the whole-body counting principle. Integration yields the possibility of subtracting background from renograms to calculate single renal clearances. The method offers advantages in cases of reduced measurement geometry and/or low count rates. (orig.)

This study examined 40 patients: 34 have pulmonary tuberculosis, 3 have pneumonitis, 2 have lung cancer, and one has bilharziasis. All patients have been imaged using radioisotopes compounds (99mTc-infecton and 99mTcHIG) and after 1 hour and 4 hours of patients injection.Using 99mTc-infecton gave positive results in 30 pulmonary tuberculosis patients out of 34, the 3 pneumonitis patients, while using 99mTcHIG gave positive results in 27 pulmonary tuberculosis patients including the 3 pneumonitis patients. Both 99mTc-infecton and 99mTcHIG gave negative results with the lung cancer patients and unreal positive results with the bilharziasis patient. It has been found that the sensitivity and accuracy in the examinations using 99mTc-infecton were 88%, 93%, and 85.7% respectively in comparison with using 99mTcHIG where the values were 70.6%, 91%, and 68.5% respectively. Continuing examination and monitoring of 18 tuberculosis patients for 2-18 months with anti-pulmonary tuberculosis treatment, showed complete response of 12 patients using 99mTc-infecton, and 8 by using 99mTcHIG. As a result, 99mTc-infecton can be used for examining pulmonary tuberculosis patients

The usefulness of TF for detection of breast cancer was investigated and compared with Tc-99m Sestamibi(MIBI). We performed scintimammography(SM) in a total of 55 patients with breast tumors, 28 patients underwent MIBI SM other 27 patients underwent TF SM. Sensitivity, specificity, and accuracy values obtained with MIBI and TF SM for breast cancer were 73.7%, 58.9%, 83.9% and 70.6%, 61.1% and 83.3%, respectively. Also we investigated whether early imaging with TF may be used for evaluating Pgp status in breast cancer patients. Fifteen patients with breast cancer were evaluated. Tumor/background ratio(T/Bg) and washout rates(WR) were calculated, which were compared with the amount of Pgp staining in tumour cells. The average WR were 0.35±0.09. The WR demostrated significant correlation with the amount of Pgp expression (rho=0.73, p<0.01). TF was effective in detecting breast cancer. TF washout at 1hr showed good correlation with the amount of Pgp. Thus 1hr delay imaging with TF may suffice for evaluating Pgp status in breast cancer patients

In anesthetized rabbits we measured clearance from lung to blood of eight aerosolized technetium-99m-labeled compounds: diethylenetriaminepentaacetate (99mTc-DTPA); cytochrome c; myoglobin; a myoglobin polymer; albumin; and anionic, cationic, and neutral dextrans of equivalent molecular size. We investigated the effect of applying positive end-expiratory pressure (PEEP) and, on a subsequent occasion, of injecting oleic acid intravenously to produce acute lung injury on the pulmonary clearance rate. Base-line clearance rates were monoexponential and varied with the molecular weights of the radiotracers. For each tracer the rate of clearance was increased a similar degree by either PEEP or oleic acid. However, with PEEP, clearance remained monoexponential, whereas after oleic acid, smaller molecular-weight radiotracers had multiexponential clearancecurves. This suggests that after oleic acid the alveolar epithelium breaks down in a nonuniform fashion. We conclude that differentiation of the effect of PEEP from that of severe lung injury caused by oleic acid is not readily accomplished by either increasing the size of the tracer molecule or by varying the molecular charge

Using parts of the molecular structure of spiperone, two new ligand systems for complexation with [99mTc]technetium were prepared in order to develop potential receptor imaging agents for single photon emission computer tomography (SPECT). The bis-aminoethanethiols (BAT): 1-benzyl-4-(2-mercapto-2-methyl-4-aza-pentyl)-4-(2-mercapto-2-methyl- propylamino)-piperidine (benzylpiperidyl-BAT, BP-BAT) and 1-[3-(4-fluorobenzoyl)-propyl]-4-(2-mercapto-2-methyl-4-aza-pentyl)-4-(2- mercapto-2-methyl-propylamino)-piperidine (butyrophenoylpiperidyl-BAT, BUP-BAT) form stable, neutral and lipid soluble complexes with [99mTc]technetium at pH ≥ 11 using SnCl2 as reducing agent in nearly quantitative radiochemical yields. Biodistribution of 99mTc-BP-BAT and 99mTc-BUP-BAT in rats showed a moderate clearance from blood and low uptake and retention in the liver, whereas brain uptake was moderate, however with prolonged brain retention. On the other hand, significant accumulations and retentions were observed in heart, kidney and lung with increasing oxygen/blood ratios up to 24 h. Within 24 h p.i. 22 and 29% of the injected dose (i.d.) of 99mTc-BP-BAT and 99mTc-BUP-BAT were eliminated by hepatobiliary excretion whereas 22% i.d. of both 99mTc-BAT complexes were excreted into the urine. Although first biodistribution studies of 99mTc-BP-BAT and 99mTc-BUP-BAT in rats showed relatively low brain uptake, the high uptake in peripheral, receptor rich organs indicates that compounds of this type may be used as a basis for further structural modification to develop agents with optimal properties for cerebral or peripheral receptor imaging with SPECT

In this study, we present the evaluation of two new ternary ligand {sup 99m}Tc complexes [{sup 99m}Tc(HYNIC tetramer)(tricine)(L)] [L=isonicotinic acid (ISONIC) and 2,5-pyridinedicarboxylic acid (PDA)] as potential radiotracers for tumor imaging. Athymic nude mice bearing MDA-MB-435 human breast cancer xenografts were used to evaluate their biodistribution and metabolic properties. Solution stability data showed that [{sup 99m}Tc(HYNIC tetramer)(tricine)(L)] (L=ISONIC and PDA) had significant decomposition (14% and 35%, respectively) at 6 h in the absence of excess ISONIC or PDA coligand. Biodistribution data clearly showed that [{sup 99m}Tc(HYNIC tetramer)(tricine)(PDA)] had a much lower uptake in most organs of interest than [{sup 99m}Tc(HYNIC tetramer)(tricine)(ISONIC)] during the 2-h study period. Results from metabolism studies revealed that {approx}50% of [{sup 99m}Tc(HYNIC tetramer)(tricine)(ISONIC)] remained intact in fecal samples at 120 min postinjection, whereas only 10% of [{sup 99m}Tc(HYNIC tetramer)(tricine)(PDA)] remained intact in fecal samples. The extent of metabolism correlated well with radiotracer solution stability. The results from this and our previous studies clearly demonstrated that coligands [trisodium triphenylphosphine-3,3',3''-trisulfonate (TPPTS), ISONIC and PDA] have a significant impact on the tumor uptake, excretion kinetics and metabolism of the {sup 99m}Tc-labeled cyclic RGDfK tetramer. Among the three radiotracers evaluated in this tumor-bearing animal model, [{sup 99m}Tc(HYNIC tetramer)(tricine)(TPPTS)] remained the best with respect to blood clearance, tumor uptake and target/background ratios.

In this study, we present the evaluation of two new ternary ligand 99mTc complexes [99mTc(HYNIC tetramer)(tricine)(L)] [L=isonicotinic acid (ISONIC) and 2,5-pyridinedicarboxylic acid (PDA)] as potential radiotracers for tumor imaging. Athymic nude mice bearing MDA-MB-435 human breast cancer xenografts were used to evaluate their biodistribution and metabolic properties. Solution stability data showed that [99mTc(HYNIC tetramer)(tricine)(L)] (L=ISONIC and PDA) had significant decomposition (14% and 35%, respectively) at 6 h in the absence of excess ISONIC or PDA coligand. Biodistribution data clearly showed that [99mTc(HYNIC tetramer)(tricine)(PDA)] had a much lower uptake in most organs of interest than [99mTc(HYNIC tetramer)(tricine)(ISONIC)] during the 2-h study period. Results from metabolism studies revealed that ∼50% of [99mTc(HYNIC tetramer)(tricine)(ISONIC)] remained intact in fecal samples at 120 min postinjection, whereas only 10% of [99mTc(HYNIC tetramer)(tricine)(PDA)] remained intact in fecal samples. The extent of metabolism correlated well with radiotracer solution stability. The results from this and our previous studies clearly demonstrated that coligands [trisodium triphenylphosphine-3,3',3''-trisulfonate (TPPTS), ISONIC and PDA] have a significant impact on the tumor uptake, excretion kinetics and metabolism of the 99mTc-labeled cyclic RGDfK tetramer. Among the three radiotracers evaluated in this tumor-bearing animal model, [99mTc(HYNIC tetramer)(tricine)(TPPTS)] remained the best with respect to blood clearance, tumor uptake and target/background ratios

In children who have undergone both 99mTc-DMSA and 99mTc-MAG3 studies for the assessment of differential renal function (DRF) and drainage, respectively, we have noticed good agreement between the calculated DRF values, and hypothesized that there is no significant difference in DRF values calculated from these tests. Therefore, both tests may not always be necessary. To determine whether there is a statistically significant difference between DRF values calculated using 99mTc-DMSA and those calculated using 99mTc-MAG3. We retrospectively identified children imaged with 99mTc-DMSA and 99mTc-MAG3. We recorded DRF values, age, indication, and renal pelvis diameter. For the 99mTc-DMSA studies we recorded the imaging time after injection. For the 99mTc-MAG3 studies we recorded the delay between injection and data acquisition, diuretic use and evidence of delayed drainage or reflux. We identified 100 episodes in 92 children where both 99mTc-DMSA and 99mTc-MAG3 scans had been performed within a few days. The commonest indication was urinary tract infection or pelviureteric junction obstruction. The mean age of the children was 6.96 years. A significant but clinically acceptable trend was seen between abnormal DRF and difference between tests. A significant link was found with the difference between tests and the time of imaging after DMSA injection, and also with scarring. No significant effect was caused by renal pelvis dilatation, delayed drainage, frusemide administration, or delayed 99mTc-MAG3 imaging. If a 99mTc-MAG3 study has been performed then a 99mTc-DMSA study is unnecessary provided DRF is normal on the 99mTc-MAG3 study and there is no scarring. A change in practice would lead to considerable savings in time, cost and radiation burden. (orig.)

textabstractIt is established that in a wide variety of acute and chronic lung diseases the integrity of the alveolar-capillary membrane is altered. Increased permeability of the barrier is thought to cause increased filtration of fluids and proteins into the alveoli and increased absorption of inhaled substances into the blood stream. This can eventually lead to impaired gas exchange and, therefore, deterioration of tissue oxygenation. Attempts to elucidate the nature of changes occurring in...

[111In-diethylene triamine penta-acetic acid-d-Phe1]-octreotide (DTPA-octreotide) scintigraphy has gained widespread acceptance as a diagnostic clinical procedure in oncology for imaging somatostatin receptor-positive tumours. However, indium-111 as a radiolabel has several drawbacks, including limited availability, suboptimal gamma energy and high radiation burden to the patient. We have recently reported on the preclinical development of 99mTc-EDDA/HYNIC-TOC, a new octreotide derivative which showed promising results both in vitro and in vivo. We now report our initial clinical experiences with this new radiopharmaceutical in ten oncological patients. The clinical diagnoses were: carcinoid syndrome (n=5), thyroid cancer (n=3), pancreatic cancer (n=1) and pituitary tumour (n=1). The biodistribution and kinetics of 99mTc-EDDA/HYNIC-TOC were compared with those of 111In-DTPA-octreotide in six cases, and with those of 111In-DOTA-TOC in five cases. With the new tracer tumours were imaged within 15 min after injection and showed the highest target/non-target ratios 4 h after injection. Tumour uptake persisted up to 20 h p.i. The rate of blood clearance was similar to that of 111In-DTPA-octreotide but faster than that of 111In-DOTA-TOC, while urinary excretion was lower compared with the 111In derivatives. Semi-quantitative region of interest analysis showed that 99mTc-EDDA/HYNIC-TOC produced higher tumour/organ (target/non-target) ratios than the 111In derivatives, especially in relation to heart and muscle. Significantly more lesions could be detected in 99mTc images. We conclude that 99mTc-EDDA/HYNIC-TOC shows better imaging properties for the identification of somatostatin receptor-positive tumour sites than currently available 111In-labelled octreotide derivatives. (orig.)

Unilateral arthritis of the knee was induced in mongrel puppies by intraarticular injections of 1% Carragheenan. Bone metabolism was studied by a scintimetric technique on static 99mTc-diphosphonate bone scans every 2nd week during the induction of arthritis for 3 months and monthly in a postarthritic phase of another 3 months. Changes in uptake of radionuclide were present after 2 weeks. The induction phase was characterized by a decreased uptake in the calcification layer of the juxta-articular growth plates and a moderately increased epiphyseal uptake. The postarthritic phase was characterized by normalization of growth plate uptake and a marked increase in epiphyseal uptake. Using contact autoradiography, the epiphyseal uptake was seen mainly in a narrow subchondral and subsynovial bone layer, around bone cysts and osteophytes, whereas central epiphyseal bone was osteopenic with decreased uptake of tracer. The study suggests that the early scintigraphic appearance of juvenile non-suppurative arthritis may be an overall decrease in uptake of 99mTc-diphosphonate due to a depression of growth plate metabolism. (author)

Preparations of d,l- and meso-hexamethylpropyleneamine oxime (HM-PAO) labeled with technetium-99m were added to rat brain homogenates diluted with phosphate buffer (1:10). The conversion of d,l-HM-PAO to hydrophilic forms took place with an initial rate constant of 0.12 min-1. Incubation of the...... chromatographic characteristics as found in the brain homogenates. The rate constant for the conversion reaction of d,l-HM-PAO in GSH aqueous solution was 208 and 317 L/mol/min in two different assay systems and for meso-HM-PAO the values were 14.7 and 23.2 L/mol/min, respectively. Rat brain has a GSH...... correspondence of values supports the notion that GSH may be important for the in vivo conversion of 99mTc-labeled HM-PAO to hydrophilic forms and may be the mechanism of trapping in brain and other cells. A kinetic model for the trapping of d,l- and meso-HM-PAO in tissue is developed that is based on data of...

99m technetium pyrophosphate myocardium scintigraphy is a very recent examination technique. This work gives the results obtained on 61 patients. As a vector of the isotope, pyrophosphate has the advantage over polyphosphate of a fast bone uptake there it should be stressed that a 90 minute pause is necessary between the intraveinous injection of the isotope and the photographic recording so that the reading is not troubled by the labelled intracardiac blood pool image, an image quality criterion being the estimation of a good costal fixation which in fact appears sooner or later according to the subject. The role of pyrophosphate, chelator of calcium in fixation of the isotope on the myocardium, could be explained by the fast appearance of 'dense bodies', made up of calcium hydroxyapathice crystals, in the mitochondria of myocardium cells having undergone an irreversible necrotic process. The choice of 99m technetium is based on its ease of use: 6 hour half-life, high-energy pure gamma emission at 140 keV. The fixed image studied under two incidences, front and left anterior oblique, is obtained from mobile images given by the scintillation camera used in connection with a data processing system. Several facts are underlined, explaining the disadvantages, advantages and indications of the method

Technetium-99m galactosyl-neoglycoalbumin ( [Tc]NGA) is a radiolabeled ligand to hepatic binding protein, a receptor which resides at the plasma membrane of hepatocytes. This receptor-binding radiopharmaceutical and its kinetic model provide a noninvasive method for the assessment of liver function. Eighteen patients were studied: seven with hepatoma, eight with liver metastases, four with cirrhosis, and one patient with acute fulminant non-A, non-B hepatitis. Technetium-99m NGA liver imaging provided anatomic information of diagnostic quality comparable to that obtained with other routine imaging modalities, including computed tomography, angiography, ultrasound, and [Tc]sulfur colloid scintigraphy. Kinetic modeling of dynamic [Tc]NGA data produced estimates of standardized hepatic blood flow, Q (hepatic blood flow divided by total blood volume), and hepatic binding protein concentration, [HBP]. Significant rank correlation was obtained between [HBP] estimates and CTC scores. This correlation supports the hypothesis that [HBP] is a measure of functional hepatocyte mass. The combination of decreased Q and markedly reduced [HBP] may have prognostic significance; all three patients with this combination died of hepatic failure within 6 wk of imaging

In the field of diagnostic imaging, the concept of imaging hypoxia constitutes an important development and 99mTc labelled vectors have taken a long stride in this direction. Delineation of hypoxic cells amidst oxygenated cells has a strong bearing on treatment strategies and regimes, since hypoxic cells are normally resistant to therapy, thus having a direct influence on the extent of tumour propagation and malignant progression. Inherent drawbacks in the invasive methods currently available for measuring hypoxia led to the development of non-invasive modalities such as use of radiolabelled molecules for imaging hypoxia. In the chapter, an attempt is made to provide a comprehensive overview of 99mTc based radiopharmaceutical agents as well as a brief discussion of other radiolabelled agents that show considerable promise in diagnostic imaging of tumour hypoxia. The review also discusses the phenomenon of hypoxia, other non-invasive methods of detecting hypoxia currently available and the evolution of radiopharmaceuticals to image hypoxia. (author)

Acute renal failure is a common complication of kidney transplantation. The major causes are acute tubular necrosis (ATN), arterial or venous thrombosis, rejection, ureteral obstruction, and extravasation. Each situation requires a different treatment and demands prompt diagnosis to prevent loss of the graft and patient morbidity or mortality. The clinical problem is further complicated by the possible coincidence of more than one of these pathologies, in particular the development of graft rejection superimposed on ATN in the post-transplant period. The diagnostic studies used in this differential diagnosis may include retrograde ureteral catheterization, renal arteriography, open or closed renal biopsy, isotope studies with 133xenon, 131I-hippuran, 203Hg-chlormerodrin, and more recently /sup 99m/pertechnetate. Only the latter methods with hippuran, chlormerodrin, and pertechnetate avoid direct manipulation of the graft or its artery or ureter with the inherent risks of such procedures. We present results of serial studies of sodium /sup 99m/pertechnetate photoscanning(Tc scan) in 38 renal homografts. In some studies computer determined graphs of renal radioactivity versus time (Tc renogram) were obtained

Radiopharmaceuticals are widely used in nuclear medicine. The comprehension of their uptake mechanism in target organs, as well as their clearance may depend on the elucidation of their biochemical characteristics, for instance, their binding to blood elements. The reported precipitating studies of blood with radiopharmaceuticals have shown that the results can not be easily compared. Then, we decide evaluate of the binding proteins on the blood elements using trichloroacetic acid (TCA) to determine the radioactivity of the dimercaptosuccinic acid with technetium-99m (99mTc-DMSA) present in precipitating plasma (P) and blood cells (BC). Depending on the TCA concentration we have determined different values in the insoluble fractions of the plasma when the in vivo and in vitro evaluations were carried out. (author)

On the basis of the high specificity of the antigen-antibody reaction, tumor antigens can be recognized in vivo by specific antibodies, labelled with gamma emitting radionuclides (I-131, I-123, In-111, Tc-99m). Immunoscintigraphic detection of different human tumours has been obtained. A further improvement in the technique has been produced by the use of labelled purified FAb fragments, i.e. without Fc, the main cause of aspecific bonds. Divalent fragments, F(ab')2, have a better target/background ratio and show a faster clearance rate from the blood pool. Here we present our experience using Tc-99m-F(ab')2 of the 225.28S monoclonal antibody that recognizes high molecular weight melanoma associated antigens (HMW-MAA). (Auth.)

For the purpose of developing novel diagnostic pharmaceuticals of 99mTc-labeled small-size complexes, six novel complexes of 99mTc-2-hydroxybenzaldehyde-amino acid Schiff bases were designed and synthesized, and their biodistributions in mice were investigated. All the compounds were obtained in radiochemical yields higher than 90% at optimal conditions, and poor uptakes in muscle, brain, heart and tumor were commonly observed with rapid blood clearance. Potentiality was revealed of good kidney imaging by 2-hydroxybenzaldehyde-alanine (L2) complex within 40 min post-injection. Good bone uptake of 2-hydroxybenzaldehyde-histidine (L4) and 2-hydroxybenzaldehyde-aspartic acid (L5) complexes, high spleen accumulation of 2-hydroxybenzaldehyde-glycine (L1) and 2-hydroxybenzaldehyde-cysteine (L3) complexes, and non-specific biodistribution of 2-hydroxybenzaldehyde-glutamic acid (L6) complex were demonstrated

chest dogs (group A) these indicators were administered separately as bolus injections into a cannulated diagonal branch of the left anterior descending coronary artery (LAD) and the curve of the response function was recorded by external activity registration. In further experiments on closed and open...... chest dogs (group B) 99mTc-DTPA was injected via a coronary angiography catheter into the ostium of the left coronary artery and the response curve was obtained by external registration. Regional myocardial perfusion coefficients were determined by the local 133xenon washout technique and from kinetic...... analysis of SIRD experiments. Plasma perfusion coefficients calculated by kinetic analysis of response curves from 99mTc-DTPA SIRD experiments (group A) were on average 98 v 102 ml.min-1.100 g-1 in 51Cr-EDTA experiments, in good agreement with the average plasma flow rate of 92 ml.min-1.100 g-1 determined...

The purpose of this study was to investigate the differences between technetium-99m ethyl cysteinate dimer (99mTc-ECD) and technetium-99m hexamethylpropylene amine oxime (99mTc-HMPAO) uptake in the same brains by means of statistical parametric mapping (SPM) analysis. We examined 20 patients (9 male, 11 female, mean age 62±12 years) using 99mTc-ECD and 99mTc-HMPAO single-photon emission tomography (SPET) and magnetic resonance imaging (MRI) of the brain less than 7 days after onset of stroke. MRI showed no cortical infarctions. Infarctions in the pons (6 patients) and medulla (1), ischaemic periventricular white matter lesions (13) and lacunar infarction (7) were found on MRI. Split-dose and sequential SPET techniques were used for 99mTc-ECD and 99mTc-HMPAO brain SPET, without repositioning of the patient. All of the SPET images were spatially transformed to standard space, smoothed and globally normalized. The differences between the 99mTc-ECD and 99mTc-HMPAO SPET images were statistically analysed using statistical parametric mapping